OBJECTIVE Acetaminophen(APAP),also known as paracetamol,is a commonly used antipyretic,anal⁃gesic and anti-inflammatory drug.However,during the use of APAP for more than half a century,people have not only used APAP t...OBJECTIVE Acetaminophen(APAP),also known as paracetamol,is a commonly used antipyretic,anal⁃gesic and anti-inflammatory drug.However,during the use of APAP for more than half a century,people have not only used APAP to fight diseases but have also suffered the adverse effects brought about by APAP for more than half a cen⁃tury.The most serious adverse reaction to APAP is hepatotoxicity caused by overdose or long-term use.In Chinese tra⁃ditional medicine,chrysanthemums have the functions of dispelling wind,dissipating heat,clearing the liver and improv⁃ing eyesight.Although the chrysanthemum variety named Bianliang ziyu from Kaifeng is not a medicinal variety,it has good value for medicine and food.The aim of this study was to investigate the protective effect of Bianliang Ziyu extract(BZE)on APAP-damaged rats and the potential molecular mechanism.METHODS Male Sprague-Dawley rats(200-220 g)were intragastrically administered BZE(110,220 and 440 mg·kg^-1)for 8 d.On the ninth day,APAP(800 mg·kg^-1)was administered intragastrically to the rats 0.5 h after BZE administration to induced drug-induced liver injury.The serum and liver samples were collected after 24 h.The levels of alanine aminotransferase(ALT),aspartic aminotransferase(AST),reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in serum and liver tissue of rats were detected by kit method.HE staining was used to observe the histopathological changes in the liver of rat.The effects of BZE on the expression of the oxidative stress related proteins and the mitochondrial biosyn⁃thesis related proteins were detected by Western blot.RESULTS The results showed that BZE significantly reduced the levels of ALT,AST,MDA and ROS and increased the levels of GSH and SOD caused by APAP.Moreover,BZE increased phosphorylation of AMP-activated protein kinase(AMPK)and glycogen synthase kinase 3β(GSK3β),promoted the nuclear translocation of nuclear factor-erythroid 2-related factor 2(Nrf2).BZE also upregulated the expression of mitochondrial biosynthesis related proteins such as peroxisome proliferator-activated receptorγ(PPAR-γ),peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α),mitochondrial transcription factor(TFAM)and nuclear respira⁃tory factor 1(NRF1).CONCLUSION BZE alleviates APAP-induced liver injury in rats by inhibiting oxidative stress via GSK3β-Nrf2 signaling and the mitochondrial biosynthesis pathway mediated by AMPK.展开更多
OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabol...OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabolic syndrome.The emerging evidence support the use of prebiotics like herb-derived polysaccharides for treating NAFLD by modulating gut microbiome.So,our study focused on the microbiota-dependent anti-NAFLD effect and the exact mechanisms of Astragalus polysaccharides(APS)extracted from Astragalus mongholicus Bunge in high-fat diet(HFD)fed mice.METHODS Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS.Then,targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids(SCFAs)and bacteria that were specifically enriched by APS.Further in vitro experiment was carried out to test the capacity of SCFAs-producing of identified bacterium.Finally,the anti-NAFLD efficacy of identified bacterium was tested in HFD fed mice.RESULTS Our results first demonstrated the anti-NAFLD effect of APS in HFD fed mice and the contribution of gut microbiota.Moreover,our results indicated that SCFAs,predominantly acetic acid were elevated in APS-supplemented mice and ex vivo experiment.Metagenomics revealed that D.vulgaris from Desulfovibrio genus was not only enriched by APS,but also a potent generator of acetic acid,which showed significant anti-NAFLD effects in HFD fed mice.In addition,D.vulgaris modulated the hepatic gene expression pattern of lipids metabolism,particularly suppressed hepatic fatty acid synthase(FASN)and CD36 protein expression.CONCLUSION APS enriched D.vulgaris is effective on attenuating hepatic steatosis possibly through producing acetic acid,and modulation on hepatic lipids metabolism in mice.Further studies are warranted to explore the long-term impacts of D.vulgaris on host metabolism and the underlying mechanism.展开更多
OBJECTIVE Liver fibrosis is a chronic damage process related to the further progression of hepatic cirrhosis and has yet no truly effective treatment is available.This study aimed to investigate the effects of isochlo...OBJECTIVE Liver fibrosis is a chronic damage process related to the further progression of hepatic cirrhosis and has yet no truly effective treatment is available.This study aimed to investigate the effects of isochlorogenic acid A(ICQA)on liver fibrosis induced by carbon tetrachloride(CCl4)and clarify the underlying mechanism.METHODS Rats were treated with CCl4 for eight weeks in order to induce liver fibrosis and simultaneously orally administered with ICQA(10,20 and 40 mg·kg-1).RESULTS ICQA had significant protective effect on liver injury,inflammation,and fibrosis in rats.Meanwhile,ICQA prevented the activation of hepatic stellate cells(HSC)as indicated by inhibiting the overexpres⁃sion of a-smooth muscle actin(a-SMA).In addition,reduced fibrosis was found to be associated with decreased protein expression of high-mobility group box 1(HMGB1)and toll like receptor(TLR)4.Moreover,ICQA supressed the cytoplasmic translocation of HMGB1 in rat liver.Further investigations indicated that ICQA treatment significantly attenuated nuclear translocation of the nuclear factor-κB(NF-κB)p65 and inhibited degradation of IkBa expression in the liver of rats with liver fibrosis.CONCLUSION ICQA has hepatoprotective and anti-fibrotic effects in rats with liver fibrosis through modulating the HMGB1/TLR4/NF-κB signaling pathways.展开更多
OBJECTIVE Oxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis,a common consequence of chronic liver injury of multiple etiology.Nuclear factor erythroid 2-related fa...OBJECTIVE Oxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis,a common consequence of chronic liver injury of multiple etiology.Nuclear factor erythroid 2-related factor 2(Nrf2)serves as a major regulator of a celular defense system against oxidative stress.Xiaochaihutang(XCHT),a compound of seven botanical extracts used for liver diseases traditionally in East Asia.However,few studies have investigated its anti-hepatic fibrosis effects and pathophysiological mechanism of action.The present study was designed to confirm the anti-hepatic fibrosis effects and explore its potential mechanism of action by investigating the intervention of Nrf2 pathway.METHODS Liver fibrosis was induced by repeated injection of Carbon tetrachloride(CCl4) over a period of 9 weeks.Starting from the 6 th week,the animals in treatment groups were given the appropriate dose of XCHT granules and silybin.Biochemical parameters,histological changes of the liver and alpha-smooth muscle actin(α-SMA) were determined.The expressions of Nrf2,Keap1,Nqo1,HO-1,Gclc and Gclm were assessed by RT-PCR and Western blot.RESULTS CCl4 caused a significant fibrosis damage in the rat liver and the liver functions and fibrosis degree were significantly improved by XCHT(5 g·kg^(-1) and 10 g·kg^(-1)).XCHT(5 g·kg^(-1) and 10 g·kg^(-1)) treatment significantly decreased the number of cells labeled with α-SMA antibodies.Moreover,XCHT(5 g·kg^(-1) and 10 g·kg^(-1))significantly increase Nqo1,HO-1,Gclc and Gclm expressions in the liver.CONCLUSION T hese studies establish XCHT is a potentially useful therapeutic agent for treatment of hepatic fibrosis and it might be via regulation of Nrf2 pathway in rats against oxidative stress,making further efforts to inhibiting the activated HSCs.Activation or up-regulation of Nrf2 pathway may be an alternative treatment strategy for liver fibrosis.展开更多
Objective To study the damage of liver function after transcatheter arterial chemoembolization (TACE) with low-dose versus conventional-dose anticancer drugs in patients with hepatocellular carcinoma (HCC). Methods On...Objective To study the damage of liver function after transcatheter arterial chemoembolization (TACE) with low-dose versus conventional-dose anticancer drugs in patients with hepatocellular carcinoma (HCC). Methods One hundred and twelve patients with unresectable HCC were randomly divided into two groups (A and B) to receive superselective TACE. Low-dose anticancer drugs including mitomycin C (MMC) 2 ～ 8 mg,epirubicin (EPI) 5 ～ 10 mg and carboplatin (CBP) 100 mg were used in group A (n = 52),and conventional-dose of anticancer drugs (MMC 10 mg,EPI 40 mg and CBP 300 mg)for patients in group B(n = 60). Lipiodol-anticancer drugs emulsion was injected into the feeding arteries of tumor and then followed by embolization of gelatin sponge (GS) or polyvinyl alcohol (PVA) particles. Laboratory examination of the liver function including Child-Pugh scores,total bilirubin (TBIL),albumin (ALB) and alanine aminotransferase (ALT) were evaluated respectively before TACE and at third day,one week and four weeks after this procedure. Results In both groups,TBIL,ALT,and Child-Pugh scores increased (P < 0.001 or P < 0.05) and ALB decreased (P < 0.001 or P < 0.01) at three days and one week after TACE. Four weeks after-procedure,all the parameters described above showed no significant difference than those before the procedure in group A (P > 0.05). On the contrary in group B,a significant difference (P < 0.05) was found in the comparison of these parameters (except ALT). Conclusion Superselective TACE with low-dose anticancer drugs may induce transient impairment of liver function in the patients with HCC,but those patients used conventional-dose of anticancer drugs frequently cause lasting and more serious worsening of liver function. (J Intervent Radiol,2006,15: 351-355)展开更多
OBJECTIVE To study the protection effects and mechanisms of NYG-1 on CCl4-induced acute liver injury.METHODS Acute liver injury model of rats was established by using CCl4.48 male SPF SD rats were weighed and randomly...OBJECTIVE To study the protection effects and mechanisms of NYG-1 on CCl4-induced acute liver injury.METHODS Acute liver injury model of rats was established by using CCl4.48 male SPF SD rats were weighed and randomly divided into six groups with 8 in each group,normal group,model group,positive control group(silibinin),low-,medium-and high-dose NYG-1 group.Silibinin was given orally to rats in the positive control group,NYG-1(high-,medium-and low-dose)was given orally in the high-,medium-and low-dose NYG-1group,respectively.Those rats were administered appropriately according to the group once daily for seven consecutive days.On the seventh day,rats were treated with 10% CCl4(10mL·kg-1 of0.1% CCl4 solution in olive oil)intraperitoneally injecting(ip)to induce acute liver injury,except the normal group.At 16 h after CCl4 treatment,rats were weighed,then anaesthed with ether,the blood and liver were collected.Serum ALT,AST,LDH and ALP were measured.MDA content and SOD activity in liver homogenate were detected.The histopathological changes of liver were observed by H&E staining.RESULTS Acute liver injury model was established successfully in rats by intraperitoneally injecting CCl4.Pretreatment with medium and high dose NYG-1 decreased the increase of ALT,AST and MDA induced by CCl4,but it had no influence on serum LDH,ALP level and SOD activity in the liver homogenate.CONCLUSION The obtained results suggest that oral administration of NYG-1 hasve the protective effects against CCl4-induced acute hepatic injury in rats,Its mechanism may be related to antioxidant-like action.展开更多
The present experiment was performed with the objective of examining the effects of copper sources and levels on hydrogen peroxide(H_2O_2) generation by mitochondria from broiler hepatocytes. Treatments were applied t...The present experiment was performed with the objective of examining the effects of copper sources and levels on hydrogen peroxide(H_2O_2) generation by mitochondria from broiler hepatocytes. Treatments were applied to compare sources of copper(CuSO_4 versus Cu-Met) and 4 levels of dietary Cu (11,110,220 and 330 mg/kg).Day-old broilers(Cobb 500,Gallus domesticus,n=288) were randomly divided into 8 groups of 36 each and fed diets as follows:Controls(Cu 11 mg/kg) and high copper(Cu 110, 220,and 330 mg/kg),for 60 days under normal conditions.Sample collections were made at 12,36 and 60 days of age to investigate the changes in H_2O_2 generation by mitochondria from hepatocytes.Compared with those of the control diets,H_2O_2 generation by mitochondria in the high copper groups(110 to 330 mg/kg) of the two copper sources were increased(P<0.05 or P<0.01);At days 36 and 60,H_2O_2 generation by hepatic mitochondria from Cu-Met supplementation exceeded that from birds supplemented with CuSO_4 (P<0.05 or P<0.01).In addition,H_2O_2 generation by mitochondria from broilers fed with high dietary copper appeared to be associated with altered function of mitochondrial complexⅣ.The results indicated that dietary supplementation with copper induced oxidative stress damage in liver.At each level of copper supplementation,the organic Cu-Met led to more rapid H_2O_2 generation than did inorganic CuSO_4.The results also suggest that mitochondrial complexⅣmay be targeted under conditions of high dietary copper supplementation.展开更多
OBJECTIVE To fabricate Silymarin(SM) nanosuspensions(NSs) and evaluate their protective effect on stress-induced liver injury. METHODS SM nanosuspensions were tailored by combination of the anti-solvent precipitation ...OBJECTIVE To fabricate Silymarin(SM) nanosuspensions(NSs) and evaluate their protective effect on stress-induced liver injury. METHODS SM nanosuspensions were tailored by combination of the anti-solvent precipitation and high pressure homogenization(HPH); the formulations were optimized by central composite design. The pharmacokinetics and pharmacodynamics of SM-NSs were also performed.RESULTS In light of the quadratic mathematical equations derived from the Design of Expert Software,the optimal formulation of SM-NSs consisted of PVP 0.34% and F188 0.36%. The morphology of NSs was found to be spherical with a diameter of about 150 nm using transmission electron microscope(TEM)observation. The pharmacokinetics experiment demonstrated that oral administration of SM-NSs significantly increased its bioavailability compared to the coarse powder(Cmax: 9.03 ± 2.39 mg · L^(-1);AUMC_(0→∞):3757.35±227.19 mg·L^(-1)·h; AUC_(0→∞):171.84±26.61 mg·L^(-1)·h). In pharmacodynamics,it was found that restraint stress produced oxidative effects and increased serum AST and ALT levels in mice,both of which were significantly inhibited by SM and SM-NSs; in addition,administration of SM-NSs showed more effective prevention against acute liver injury than SM coarse suspensions(r^2=0.986,0.984,P<0.05). CONCLUSION The results suggest that fabricated SM-NSs exert potent hepatoprotective effects and attenuate restraint stress-induced liver injury. The study provides an effective approach to improving the property of SM,which can be used for treatment of liver diseases.展开更多
OBJECTIVE To investigate the hepato-protective mechanism of thymoquinone(TQ) on the development of acetaminophen(APAP)-induced liver injury.METHODS In vivo,male kunming mice were injected with a single dose of 300 mg&...OBJECTIVE To investigate the hepato-protective mechanism of thymoquinone(TQ) on the development of acetaminophen(APAP)-induced liver injury.METHODS In vivo,male kunming mice were injected with a single dose of 300 mg·kg^(-1) APAP.Some mice were pretreated with TQ(5 or 20 mg·kg^(-1))and N-acetylcysteine(NAC,300 mg·kg^(-1))2 h before APAP injection.Mice were euthanized at 2 h,6 h,12 h after APAP treatment.In vitro,human Chang liver cells were incubated with 3.125,6.25 or 12.5μmol·L^(-1) TQ,10μmol·L^(-1) SP600125 and 500μmol·L^(-1) AICAR in the presence of APAP for 24 h.Cell viability were analyzed by MTT assay,protein expressions were assessed by Western blot.RESULTS TQ pretreatment significantly reduced serum aminotransferase and increased hepatic glutathione(GSH)and glutathione peroxidase(GSH-PX)activities,while significantly inhibited interleukin-1β(IL^(-1)β)levels.TQ significantly inhibited c-Jun N-terminal kinase(JNK),extracellular signal regulated kinase(ERK)and P38 phosphorylation induced by APAP.Moreover,TQ inhibited phosphatidylinositol 3-kinase(PI3K)/mammalian target of rapamycin(m TOR)signaling activation and activated AMPK phosphorylation induced by APAP.In addition,TQ inhibited signal transducer and activator of transcription 3(STAT3)phosphorylation on APAP-induced liver injury.In vitro,APAP enhanced JNK phosphorylation and attenuated AMPK phosphorylation in Chang liver cel s,and these effects were blocked by pretreatment with TQ,SP600125(JNK inhibitor)and AICAR(AMPK activator).CONCLUSION Our findings suggest that TQ may actively prevent APAP-induced liver injury,and this effect may be mediated by JNK and AMPK signaling pathways.展开更多
Objective To evaluate the toxic effects and efficacy of the intra-arterial chrono-chemotherapy on patients with liver metastasis arised from colorectal cancer. Methods Chemotherapy of 42 patients were randomly divided...Objective To evaluate the toxic effects and efficacy of the intra-arterial chrono-chemotherapy on patients with liver metastasis arised from colorectal cancer. Methods Chemotherapy of 42 patients were randomly divided into group A (n = 20) with continuously constant arterial infusion, and group B (n = 22) with arterial chrono-modulated infusion. And the toxic effects and efficacy of two groups were compared. Results A significant difference was found in the toxic effects of digestive system between the two groups. The treatment response was similar in the two groups. Conclusions Intra-arterial chrono-chemotherapy may decrease the toxic effects and improve the life quality of these patients. (J Intervent Radiol, 2006, 15: 487-490)展开更多
The aim of the study was to investigate the hepatoprotective effects of Folium syringae(FS) extracts against ethanolinduced acute liver injury. Mice and primary hepatocytes were pretreated with FS extracts at differen...The aim of the study was to investigate the hepatoprotective effects of Folium syringae(FS) extracts against ethanolinduced acute liver injury. Mice and primary hepatocytes were pretreated with FS extracts at different dosages before ethanol administration. Transaminases, glutathione S-transferase A1 level and hepatic biochemical indices(malondialdehyde, superoxide dismutase, glutathione and glutathione peroxidase) were determined. Pretreatment with FS extracts significantly inhibited the damage caused by ethanol and the hepatoprotective effects of FS were almost similar to Silymarin that was used to treat alcoholic liver injury. GSTA1 contents in all the FS extract-treated groups were significantly different from those in the ethanol-induced acute liver injury model group(p<0.01), and similar trends were observed in transaminases and hepatic indices level both in vitro and in vivo. The results showed that FS extracts had hepatoprotective effects against ethanol-induced injury. Those effects might be related to the enhancement of antioxidant capacity of liver cells, and FS extracts could reduce the release of liver GSTA1, which contributed to improve liver detoxification.展开更多
OBJECTIVE To prepare gingerol dropping pills and to investigate its protective effect on alcoholic liver injury. METHODS The prescription was selected by orthogonal design method and the effect of the option and ratio...OBJECTIVE To prepare gingerol dropping pills and to investigate its protective effect on alcoholic liver injury. METHODS The prescription was selected by orthogonal design method and the effect of the option and ratio of ground substance,the temperature of drug. The hardness,circular degree,the tail formation and the dissolution time were studied. Totally 40 KM mice were randomly divided into control group,model group,gingerol dropping pill group(400 mg·kg^(-1)·d^(-1)) and positive control group(bifendate,150 mg·kg^(-1)·d^(-1)) of 10 mice each. The mice from the model and two drug groups were administrated with liqueur[0.15 mL/(10 g·d)]daily by gavage for 3 weeks,Two hours later,drug group mice were treated corresponding gingerol dropping pill and bifendate. Meanwhile,the control group were gavaged same amount of normal saline. Finally,when the model of acute alcoholic liver injury was established on the 22 stday,Biochemical indicators of ocular blood in mice were observed.We also observed the change of liver morphology. RESULTS Under optimum conditions,we can obtain dropping pills having circular shape,touching with hardness and short dissolution time. Compared with the control group,the levels of alanine transaminase(ALT),glutamic-oxaloacetic transaminase(AST) and malondialdehyde(MDA) in model group were obviously increased(P<0.01),While the activity of Superoxide dismutase(SOD) were decreased. In addition,In model group,mice liver disorders,hepatic lobule fusion,accompanying a large number of patchy sample liver cell vacuoles,various sizes of fat vacuoles appeared in cytoplasm and inflammatory cell infiltration were visible around the central vein. On the contrary,compared with the model group,drug groups attenuated or even reversed hepatic pathological changes. Form gingerol dropping pill group,an increase in hepatic SOD activity and serum ALT and AST activities were found and a significant decrease in hepatic MDA content were also observed(P<0.01). CONCLUSION The prescription of gingerol dropping pills was reasonable,and the preparation process was simple. Gingerol dropping pills can protect liver from alcoholic liver injury to some extend,and the mechanism may be related to its antioxidant effect.展开更多
OBJECTIVE To investigate enhanced immune function of methionine encephalin(MENK)and its anti-tumor mechanism in CT26 colon cancer mouse model.METHODS 3×10~6CT26 cells were implanted subcutaneously in BALB/c mice....OBJECTIVE To investigate enhanced immune function of methionine encephalin(MENK)and its anti-tumor mechanism in CT26 colon cancer mouse model.METHODS 3×10~6CT26 cells were implanted subcutaneously in BALB/c mice.Four days after,MENK was peritoneally administrated at the concentration of 20 mg·kg^(-1) for 14 d.The percentage of MDSCs in bone marrow,spleen,blood,tumor and liver were detected by flow cytometry.Non-esterified fatty acid(NEFA),triglycerides(TG)and total cholesterol(T-CHO)in liver homogenate were tested by a NEFA test kit,a TG test kit and a T-CHO test kit respectively.qRT-PCR and Western blot were used to measure m RNA and protein levels of inflammation-,glycometabolsim-and lipometabolsim-associated indexes in liver.RESULTS MENK decreased percentages of MDSCs in bone marrow,spleen,blood and tumor in colon cancer mice.MENK-treated mice displayed elevated ratio of CD4^+T and CD8^+T cells in spleen as well as increased T and B lymphocytes proliferation.Meanwhile,MENK also ameliorated liver damage reflected by lower levels of GPT and GOT in serum and reduced risks of cancer-associated index including inflammation,high lipid and high glucose.Furthermore,MENK lowered down the levels of NEFA,TG and T-CHO in liver homogenate.MENK treatment decreased expression of p-STAT3,increased expression of p-AKT,IRS1 and Glut4 at protein level as well as reduced lipogenesis-associated genes and elevated glycolysis-associated genes in liver of tumor bearing mice.Also,abated expression of genes associated with MDSCs generation(M-CSF,GM-CSF,IL-6,IL^(-1)β)and migration(S100A9,KC)was observed within shrunken subcutaneous tumor by MENK intervention.CONCLUSION MENK has the ability to strength immune function against colon cancer by reducing MDSCs and improving liver metabolism.展开更多
Fatty liver in dairy cows, which is associated with decreased metabolic function of the liver, develops during times of elevated non-esterified fatty acid （NEFA） concentrations in the blood when the hepatic uptake o...Fatty liver in dairy cows, which is associated with decreased metabolic function of the liver, develops during times of elevated non-esterified fatty acid （NEFA） concentrations in the blood when the hepatic uptake of lipids exceeds the oxidation and secretion of lipids by the liver and then it will cause hepatic accumulation of triglyceride （TG）. The condition is often related to decreased health status, well-being, productivity, and reproductive performance of cows. Prevention of fatty liver in the transition period is always better than any treatments. The nutritional preventative strategies mainly focus either on decreasing the supply of NEFA to liver, and it aims to improve liver function or optimize the capacity then to dispose of NEFA by exporting them as triglycerides in lipoproteins （VLDL）. Good dry cow nutritional programs, combined with excellent feeding management to achieve high levels of dry matter intake throughout the transition period should be the first priority for management. Several different compounds can promote these metabolic actions. The addition of glucose precursors such as glycerol, propyelene glycol, or propionate salts to the feed in the transition diet can modify metabolism in a manner to decrease fatty acid mobilization from adipose tissue and reduce the likelihood of liver TG accumulation. Supplying some other specific nutrients to dairy cows during the transition period may increase rates of NEFA disposal, with resulting effects on performance, though the hepatic capacities for export as triglycerides within VLDL are relatively limited in ruminants. Further studies examining nutritional and management strategies are required to develop new preventive or treatment options that are more practical to reduce the occurrence of fatty liver and its adverse metabolic effects.展开更多
Aim Liver fibrosis is a consequence of chronic liver disease which can progress into liver cirrhosis evenhepatocarcinoma. FuzhengHuayu （FZHY） , a Chinese herbal formula, had been reported to have the effect of anti-...Aim Liver fibrosis is a consequence of chronic liver disease which can progress into liver cirrhosis evenhepatocarcinoma. FuzhengHuayu （FZHY） , a Chinese herbal formula, had been reported to have the effect of anti- fibrosis. This study aims to investigate the effective targets and the mechanisms of FZHY on liver fibrosis. Methods The liver tissue samples of normal group, model group and FZHY-treated group were examined by microarray and iTRAQ. Profiles of differentially expressed genes （DEGs） and differentially expressed proteins （DEPs） in CC14-in- duced liver fibrosis model in rat were analyzed. GO and Pathway were analyzed by DAVID, and protein-protein in- teraction （PPI） was analyzed by STRING and cytoscape. The targets of FZHY compounds were predicted by TCM- SP. Results The results showed that 255 genes （ fold change ≥ 1.5, P 〈 0.05） and 507 proteins （ fold change ≥ 1.2 ,P 〈 0.05 ） were differentially expressed between FZHY group and model group. The high-throughput data of transcriptomics and proteomics was analyzed synthetically. DAVID function annotation analysis showed that these DEGS and DEPs both enriched in 15 GO terms, among drug metabolic process, response to extracellular stimulus, response to vitamin, arachidonic acid metabolic process, response to wounding and oxidation reduction may involve in liver fibrosis. KEGG pathway analysis showed that these DEGS and DEPs both enriched in 9 pathways, among arachidonic acid metabolism, retinol metabolism, metabolism of xenobiotics by cytochrome P450 and drug metabo- lism may be related to liver fibrosis. PPI analysis found that 10 overlapped core genes and proteins, among, Ugt2a3, Cyp2bl and Cyp3al8 were of higher degree, which are all enriched in retinol metabolism. Interestedly, Cyp2bl and Cyp3al8 were also predicted with TCMSP as the targets of FZHY compounds. Conclusion The re- sults indicated that the effective mechanism of FZHY against liver fibrosis is involved in the regulation of multiple targets and multiple pathways, among, retinol metabolism pathway by targeting Ugt2a3, Cyp2bl and Cyp3al8 may play an important role in the treatment of liver fibrosis.展开更多
Nicotinic acid (N.C.)and choline were given orally to the periparturient cows to treat and prevent fatty liver.Blood parameters of glucose,β-hydroxybutyrate,albumin,total protein,magnesium,aspartate aminotransferase(...Nicotinic acid (N.C.)and choline were given orally to the periparturient cows to treat and prevent fatty liver.Blood parameters of glucose,β-hydroxybutyrate,albumin,total protein,magnesium,aspartate aminotransferase(AST)and non-esterified fatty acid (NEFA)weremeasured.There were no significant differences betWeen the treated and untreated groups in theplasma concentrations of albumin,total, protein and magnesium.Significant decrease in plasmaconcentrations of β-hydroxybutyrate,NEFA and AST were observed in the treated cows followiug administration of N.C.and choline.All the fatty liver cows(100% )treated with N.C.andcholine recovered within 5 weeks after calving compared with 71.4%(5/7) of untreated cows recovered.The incident rate of fatty liver postpartum in the cows with N.C.and cholinc given 2 weeksbefore calving was 30%(3/10),and the affected cows had a range of mild to moderate fatty liverwhilst the incident rate was 50% (5/10)in the untreated cows,which had a range of mild to ofsevere fatty liver.Meanwhile,the treated cows had a significant higher prodection of milk and shorter intervals from calving to uterine involution, to the first postpartum ovulation and to conception.展开更多
Effects of subchronic aluminum （Al） exposure on the function of rat liver were investigated in this experiment. A total of 48 male Wistar rats （4 weeks old） were randomly divided into four groups： experimental gr...Effects of subchronic aluminum （Al） exposure on the function of rat liver were investigated in this experiment. A total of 48 male Wistar rats （4 weeks old） were randomly divided into four groups： experimental groups were orally exposed to 64.18, 128.36, 256.72 mg. kg^-1 body weight aluminum trichloride （AlCl3） in drinking water, and the control group with distilled water. The experiment lasted for 120 days. The activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-PX）, the concentration of malondialdehyde （MDA） in serum and liver, and alanine transarninase （ALT） and aspartate aminotransferase （AST） activities in serum were detected in all groups. The results showed that the activities of ALT, AST in serum and the concentrations of MDA in liver in the Al-treated groups significantly increased compared with the control group; the activities of GSH-PX and SOD in high-dose Al-treated group were significantly lower than those in control group. Our findings indicated that subchronic AI exposure could result in injures of lipid peroxidation and function in liver.展开更多
Nonalcoholic fatty liver disease （NAFLD） is one of the common chronic liver disease, and may turn to cirrhosis of the liver or liver cancer, but its pathogenesis is unclear. Acanthoic acid （AA） have some improveme...Nonalcoholic fatty liver disease （NAFLD） is one of the common chronic liver disease, and may turn to cirrhosis of the liver or liver cancer, but its pathogenesis is unclear. Acanthoic acid （AA） have some improvement on drug-induced liver fibrosis, but its protective effect on Lieber-DeCarli （LD） liquid type fat diet-induced liver cell damage had less been reported, this study was conducted to determine whether acanthoic acid （AA） would a- meliorate LD-stimulated fatty liver in mice. Male C57BL/6 mice were randomly divided into six groups, including normal group, AA （40 mg · kg^-1） single group, LD-treated group, AA （20 mg· kg-1） plus LD-treated group, and AA （40 mg · kg^-1） plus LD-treated group and protive control group, they were given LD （20mL/only） , at same time gavage administration AA （20 mg · kg^-1, 40 mg· kg^-1） , while normal group were given normal diet. After 8 weeks, weighed again, then took blood by removalling eyeball, took liver. The serum aspartate aminotrans- ferase （AST）, alanine aminotransferase （ALT）, triglyceride （TG） and high density lipoprotein cholesterol （HDL- （i） in serum were determined with reagent strips. The liver was used to do Western blot, Hematoxylin ＆Eosin （H＆E） staining and Oil red staining. The Reagent results showed that administration of AA significantly inhibit the increase of AST, ALT caused by NAFLD, as well as TG and HDL-C in serum. Supplement of AA prevented LD-in- duced acidophilic necrosis, increased hepatocyte muclei and stromal inflammation infiltration as indicated by liver histopathological studies. The results indicated that AA significantly decreased the expression of SREBP-1, oL- TIMP1 and MMP-13 kept a dynamic equilibrium, TIMP1 was decreased, SMA, collagen-I, NF-KB. In addittion, while the expression of MMP-13 was increased. H＆Estaing and oil staing indicated that model group showed typical fatty degeneration, while the fatty liver histopathology of administration group showed significant improvement. These effects were associated with the down-regulation of SREBP-1 and particularly the activation of AMPK. All of these findings demostrated that AA had some improvement on LD-induced NAFLD, and its mechanism may be re- lated to SREBP1 and AMPK pathway.展开更多
文摘OBJECTIVE Acetaminophen(APAP),also known as paracetamol,is a commonly used antipyretic,anal⁃gesic and anti-inflammatory drug.However,during the use of APAP for more than half a century,people have not only used APAP to fight diseases but have also suffered the adverse effects brought about by APAP for more than half a cen⁃tury.The most serious adverse reaction to APAP is hepatotoxicity caused by overdose or long-term use.In Chinese tra⁃ditional medicine,chrysanthemums have the functions of dispelling wind,dissipating heat,clearing the liver and improv⁃ing eyesight.Although the chrysanthemum variety named Bianliang ziyu from Kaifeng is not a medicinal variety,it has good value for medicine and food.The aim of this study was to investigate the protective effect of Bianliang Ziyu extract(BZE)on APAP-damaged rats and the potential molecular mechanism.METHODS Male Sprague-Dawley rats(200-220 g)were intragastrically administered BZE(110,220 and 440 mg·kg^-1)for 8 d.On the ninth day,APAP(800 mg·kg^-1)was administered intragastrically to the rats 0.5 h after BZE administration to induced drug-induced liver injury.The serum and liver samples were collected after 24 h.The levels of alanine aminotransferase(ALT),aspartic aminotransferase(AST),reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in serum and liver tissue of rats were detected by kit method.HE staining was used to observe the histopathological changes in the liver of rat.The effects of BZE on the expression of the oxidative stress related proteins and the mitochondrial biosyn⁃thesis related proteins were detected by Western blot.RESULTS The results showed that BZE significantly reduced the levels of ALT,AST,MDA and ROS and increased the levels of GSH and SOD caused by APAP.Moreover,BZE increased phosphorylation of AMP-activated protein kinase(AMPK)and glycogen synthase kinase 3β(GSK3β),promoted the nuclear translocation of nuclear factor-erythroid 2-related factor 2(Nrf2).BZE also upregulated the expression of mitochondrial biosynthesis related proteins such as peroxisome proliferator-activated receptorγ(PPAR-γ),peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α),mitochondrial transcription factor(TFAM)and nuclear respira⁃tory factor 1(NRF1).CONCLUSION BZE alleviates APAP-induced liver injury in rats by inhibiting oxidative stress via GSK3β-Nrf2 signaling and the mitochondrial biosynthesis pathway mediated by AMPK.
基金National Natural Science Foundation of China(81873059,82004016)。
文摘OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabolic syndrome.The emerging evidence support the use of prebiotics like herb-derived polysaccharides for treating NAFLD by modulating gut microbiome.So,our study focused on the microbiota-dependent anti-NAFLD effect and the exact mechanisms of Astragalus polysaccharides(APS)extracted from Astragalus mongholicus Bunge in high-fat diet(HFD)fed mice.METHODS Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS.Then,targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids(SCFAs)and bacteria that were specifically enriched by APS.Further in vitro experiment was carried out to test the capacity of SCFAs-producing of identified bacterium.Finally,the anti-NAFLD efficacy of identified bacterium was tested in HFD fed mice.RESULTS Our results first demonstrated the anti-NAFLD effect of APS in HFD fed mice and the contribution of gut microbiota.Moreover,our results indicated that SCFAs,predominantly acetic acid were elevated in APS-supplemented mice and ex vivo experiment.Metagenomics revealed that D.vulgaris from Desulfovibrio genus was not only enriched by APS,but also a potent generator of acetic acid,which showed significant anti-NAFLD effects in HFD fed mice.In addition,D.vulgaris modulated the hepatic gene expression pattern of lipids metabolism,particularly suppressed hepatic fatty acid synthase(FASN)and CD36 protein expression.CONCLUSION APS enriched D.vulgaris is effective on attenuating hepatic steatosis possibly through producing acetic acid,and modulation on hepatic lipids metabolism in mice.Further studies are warranted to explore the long-term impacts of D.vulgaris on host metabolism and the underlying mechanism.
文摘OBJECTIVE Liver fibrosis is a chronic damage process related to the further progression of hepatic cirrhosis and has yet no truly effective treatment is available.This study aimed to investigate the effects of isochlorogenic acid A(ICQA)on liver fibrosis induced by carbon tetrachloride(CCl4)and clarify the underlying mechanism.METHODS Rats were treated with CCl4 for eight weeks in order to induce liver fibrosis and simultaneously orally administered with ICQA(10,20 and 40 mg·kg-1).RESULTS ICQA had significant protective effect on liver injury,inflammation,and fibrosis in rats.Meanwhile,ICQA prevented the activation of hepatic stellate cells(HSC)as indicated by inhibiting the overexpres⁃sion of a-smooth muscle actin(a-SMA).In addition,reduced fibrosis was found to be associated with decreased protein expression of high-mobility group box 1(HMGB1)and toll like receptor(TLR)4.Moreover,ICQA supressed the cytoplasmic translocation of HMGB1 in rat liver.Further investigations indicated that ICQA treatment significantly attenuated nuclear translocation of the nuclear factor-κB(NF-κB)p65 and inhibited degradation of IkBa expression in the liver of rats with liver fibrosis.CONCLUSION ICQA has hepatoprotective and anti-fibrotic effects in rats with liver fibrosis through modulating the HMGB1/TLR4/NF-κB signaling pathways.
文摘OBJECTIVE Oxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis,a common consequence of chronic liver injury of multiple etiology.Nuclear factor erythroid 2-related factor 2(Nrf2)serves as a major regulator of a celular defense system against oxidative stress.Xiaochaihutang(XCHT),a compound of seven botanical extracts used for liver diseases traditionally in East Asia.However,few studies have investigated its anti-hepatic fibrosis effects and pathophysiological mechanism of action.The present study was designed to confirm the anti-hepatic fibrosis effects and explore its potential mechanism of action by investigating the intervention of Nrf2 pathway.METHODS Liver fibrosis was induced by repeated injection of Carbon tetrachloride(CCl4) over a period of 9 weeks.Starting from the 6 th week,the animals in treatment groups were given the appropriate dose of XCHT granules and silybin.Biochemical parameters,histological changes of the liver and alpha-smooth muscle actin(α-SMA) were determined.The expressions of Nrf2,Keap1,Nqo1,HO-1,Gclc and Gclm were assessed by RT-PCR and Western blot.RESULTS CCl4 caused a significant fibrosis damage in the rat liver and the liver functions and fibrosis degree were significantly improved by XCHT(5 g·kg^(-1) and 10 g·kg^(-1)).XCHT(5 g·kg^(-1) and 10 g·kg^(-1)) treatment significantly decreased the number of cells labeled with α-SMA antibodies.Moreover,XCHT(5 g·kg^(-1) and 10 g·kg^(-1))significantly increase Nqo1,HO-1,Gclc and Gclm expressions in the liver.CONCLUSION T hese studies establish XCHT is a potentially useful therapeutic agent for treatment of hepatic fibrosis and it might be via regulation of Nrf2 pathway in rats against oxidative stress,making further efforts to inhibiting the activated HSCs.Activation or up-regulation of Nrf2 pathway may be an alternative treatment strategy for liver fibrosis.
文摘Objective To study the damage of liver function after transcatheter arterial chemoembolization (TACE) with low-dose versus conventional-dose anticancer drugs in patients with hepatocellular carcinoma (HCC). Methods One hundred and twelve patients with unresectable HCC were randomly divided into two groups (A and B) to receive superselective TACE. Low-dose anticancer drugs including mitomycin C (MMC) 2 ～ 8 mg,epirubicin (EPI) 5 ～ 10 mg and carboplatin (CBP) 100 mg were used in group A (n = 52),and conventional-dose of anticancer drugs (MMC 10 mg,EPI 40 mg and CBP 300 mg)for patients in group B(n = 60). Lipiodol-anticancer drugs emulsion was injected into the feeding arteries of tumor and then followed by embolization of gelatin sponge (GS) or polyvinyl alcohol (PVA) particles. Laboratory examination of the liver function including Child-Pugh scores,total bilirubin (TBIL),albumin (ALB) and alanine aminotransferase (ALT) were evaluated respectively before TACE and at third day,one week and four weeks after this procedure. Results In both groups,TBIL,ALT,and Child-Pugh scores increased (P < 0.001 or P < 0.05) and ALB decreased (P < 0.001 or P < 0.01) at three days and one week after TACE. Four weeks after-procedure,all the parameters described above showed no significant difference than those before the procedure in group A (P > 0.05). On the contrary in group B,a significant difference (P < 0.05) was found in the comparison of these parameters (except ALT). Conclusion Superselective TACE with low-dose anticancer drugs may induce transient impairment of liver function in the patients with HCC,but those patients used conventional-dose of anticancer drugs frequently cause lasting and more serious worsening of liver function. (J Intervent Radiol,2006,15: 351-355)
基金The project supported by National Natural Science Foundation of China(81303254)the Natural Science Foundation of of Hubei Provincial Department of Education(D20122402)the Scientific and Technological Project of Shiyan City of Hubei Province(ZD2012003)
文摘OBJECTIVE To study the protection effects and mechanisms of NYG-1 on CCl4-induced acute liver injury.METHODS Acute liver injury model of rats was established by using CCl4.48 male SPF SD rats were weighed and randomly divided into six groups with 8 in each group,normal group,model group,positive control group(silibinin),low-,medium-and high-dose NYG-1 group.Silibinin was given orally to rats in the positive control group,NYG-1(high-,medium-and low-dose)was given orally in the high-,medium-and low-dose NYG-1group,respectively.Those rats were administered appropriately according to the group once daily for seven consecutive days.On the seventh day,rats were treated with 10% CCl4(10mL·kg-1 of0.1% CCl4 solution in olive oil)intraperitoneally injecting(ip)to induce acute liver injury,except the normal group.At 16 h after CCl4 treatment,rats were weighed,then anaesthed with ether,the blood and liver were collected.Serum ALT,AST,LDH and ALP were measured.MDA content and SOD activity in liver homogenate were detected.The histopathological changes of liver were observed by H&E staining.RESULTS Acute liver injury model was established successfully in rats by intraperitoneally injecting CCl4.Pretreatment with medium and high dose NYG-1 decreased the increase of ALT,AST and MDA induced by CCl4,but it had no influence on serum LDH,ALP level and SOD activity in the liver homogenate.CONCLUSION The obtained results suggest that oral administration of NYG-1 hasve the protective effects against CCl4-induced acute hepatic injury in rats,Its mechanism may be related to antioxidant-like action.
基金supported by the National Natural Science Foundation of China(NSFC) awarded to Tang Zhao-xin(grant number:30671550)
文摘The present experiment was performed with the objective of examining the effects of copper sources and levels on hydrogen peroxide(H_2O_2) generation by mitochondria from broiler hepatocytes. Treatments were applied to compare sources of copper(CuSO_4 versus Cu-Met) and 4 levels of dietary Cu (11,110,220 and 330 mg/kg).Day-old broilers(Cobb 500,Gallus domesticus,n=288) were randomly divided into 8 groups of 36 each and fed diets as follows:Controls(Cu 11 mg/kg) and high copper(Cu 110, 220,and 330 mg/kg),for 60 days under normal conditions.Sample collections were made at 12,36 and 60 days of age to investigate the changes in H_2O_2 generation by mitochondria from hepatocytes.Compared with those of the control diets,H_2O_2 generation by mitochondria in the high copper groups(110 to 330 mg/kg) of the two copper sources were increased(P<0.05 or P<0.01);At days 36 and 60,H_2O_2 generation by hepatic mitochondria from Cu-Met supplementation exceeded that from birds supplemented with CuSO_4 (P<0.05 or P<0.01).In addition,H_2O_2 generation by mitochondria from broilers fed with high dietary copper appeared to be associated with altered function of mitochondrial complexⅣ.The results indicated that dietary supplementation with copper induced oxidative stress damage in liver.At each level of copper supplementation,the organic Cu-Met led to more rapid H_2O_2 generation than did inorganic CuSO_4.The results also suggest that mitochondrial complexⅣmay be targeted under conditions of high dietary copper supplementation.
基金The project supported by Natural Science Foundation of Shandong Province(ZR2014HL103,ZR2016HM21,J13LM51)Taishan Medical University Foundation(2014GCC15)the Foundation of Overseas Distinguished Taishan Scholars of Shandong Province,China
文摘OBJECTIVE To fabricate Silymarin(SM) nanosuspensions(NSs) and evaluate their protective effect on stress-induced liver injury. METHODS SM nanosuspensions were tailored by combination of the anti-solvent precipitation and high pressure homogenization(HPH); the formulations were optimized by central composite design. The pharmacokinetics and pharmacodynamics of SM-NSs were also performed.RESULTS In light of the quadratic mathematical equations derived from the Design of Expert Software,the optimal formulation of SM-NSs consisted of PVP 0.34% and F188 0.36%. The morphology of NSs was found to be spherical with a diameter of about 150 nm using transmission electron microscope(TEM)observation. The pharmacokinetics experiment demonstrated that oral administration of SM-NSs significantly increased its bioavailability compared to the coarse powder(Cmax: 9.03 ± 2.39 mg · L^(-1);AUMC_(0→∞):3757.35±227.19 mg·L^(-1)·h; AUC_(0→∞):171.84±26.61 mg·L^(-1)·h). In pharmacodynamics,it was found that restraint stress produced oxidative effects and increased serum AST and ALT levels in mice,both of which were significantly inhibited by SM and SM-NSs; in addition,administration of SM-NSs showed more effective prevention against acute liver injury than SM coarse suspensions(r^2=0.986,0.984,P<0.05). CONCLUSION The results suggest that fabricated SM-NSs exert potent hepatoprotective effects and attenuate restraint stress-induced liver injury. The study provides an effective approach to improving the property of SM,which can be used for treatment of liver diseases.
基金supported by National Natural Science Foundation of China(81660689 and 81700523)
文摘OBJECTIVE To investigate the hepato-protective mechanism of thymoquinone(TQ) on the development of acetaminophen(APAP)-induced liver injury.METHODS In vivo,male kunming mice were injected with a single dose of 300 mg·kg^(-1) APAP.Some mice were pretreated with TQ(5 or 20 mg·kg^(-1))and N-acetylcysteine(NAC,300 mg·kg^(-1))2 h before APAP injection.Mice were euthanized at 2 h,6 h,12 h after APAP treatment.In vitro,human Chang liver cells were incubated with 3.125,6.25 or 12.5μmol·L^(-1) TQ,10μmol·L^(-1) SP600125 and 500μmol·L^(-1) AICAR in the presence of APAP for 24 h.Cell viability were analyzed by MTT assay,protein expressions were assessed by Western blot.RESULTS TQ pretreatment significantly reduced serum aminotransferase and increased hepatic glutathione(GSH)and glutathione peroxidase(GSH-PX)activities,while significantly inhibited interleukin-1β(IL^(-1)β)levels.TQ significantly inhibited c-Jun N-terminal kinase(JNK),extracellular signal regulated kinase(ERK)and P38 phosphorylation induced by APAP.Moreover,TQ inhibited phosphatidylinositol 3-kinase(PI3K)/mammalian target of rapamycin(m TOR)signaling activation and activated AMPK phosphorylation induced by APAP.In addition,TQ inhibited signal transducer and activator of transcription 3(STAT3)phosphorylation on APAP-induced liver injury.In vitro,APAP enhanced JNK phosphorylation and attenuated AMPK phosphorylation in Chang liver cel s,and these effects were blocked by pretreatment with TQ,SP600125(JNK inhibitor)and AICAR(AMPK activator).CONCLUSION Our findings suggest that TQ may actively prevent APAP-induced liver injury,and this effect may be mediated by JNK and AMPK signaling pathways.
文摘Objective To evaluate the toxic effects and efficacy of the intra-arterial chrono-chemotherapy on patients with liver metastasis arised from colorectal cancer. Methods Chemotherapy of 42 patients were randomly divided into group A (n = 20) with continuously constant arterial infusion, and group B (n = 22) with arterial chrono-modulated infusion. And the toxic effects and efficacy of two groups were compared. Results A significant difference was found in the toxic effects of digestive system between the two groups. The treatment response was similar in the two groups. Conclusions Intra-arterial chrono-chemotherapy may decrease the toxic effects and improve the life quality of these patients. (J Intervent Radiol, 2006, 15: 487-490)
基金Supported by the National Natural Science Foundation of China(31472241)the Application Technology Research and Development Projects in Heilongjiang Province of China(PC13S03)
文摘The aim of the study was to investigate the hepatoprotective effects of Folium syringae(FS) extracts against ethanolinduced acute liver injury. Mice and primary hepatocytes were pretreated with FS extracts at different dosages before ethanol administration. Transaminases, glutathione S-transferase A1 level and hepatic biochemical indices(malondialdehyde, superoxide dismutase, glutathione and glutathione peroxidase) were determined. Pretreatment with FS extracts significantly inhibited the damage caused by ethanol and the hepatoprotective effects of FS were almost similar to Silymarin that was used to treat alcoholic liver injury. GSTA1 contents in all the FS extract-treated groups were significantly different from those in the ethanol-induced acute liver injury model group(p<0.01), and similar trends were observed in transaminases and hepatic indices level both in vitro and in vivo. The results showed that FS extracts had hepatoprotective effects against ethanol-induced injury. Those effects might be related to the enhancement of antioxidant capacity of liver cells, and FS extracts could reduce the release of liver GSTA1, which contributed to improve liver detoxification.
基金The project supported by Col ege Students Of Science and Technology Innovation Project of Tai'an City(2015D064)the National College Students'Innovative and Entrepreneurial Training Project(201510439078)
文摘OBJECTIVE To prepare gingerol dropping pills and to investigate its protective effect on alcoholic liver injury. METHODS The prescription was selected by orthogonal design method and the effect of the option and ratio of ground substance,the temperature of drug. The hardness,circular degree,the tail formation and the dissolution time were studied. Totally 40 KM mice were randomly divided into control group,model group,gingerol dropping pill group(400 mg·kg^(-1)·d^(-1)) and positive control group(bifendate,150 mg·kg^(-1)·d^(-1)) of 10 mice each. The mice from the model and two drug groups were administrated with liqueur[0.15 mL/(10 g·d)]daily by gavage for 3 weeks,Two hours later,drug group mice were treated corresponding gingerol dropping pill and bifendate. Meanwhile,the control group were gavaged same amount of normal saline. Finally,when the model of acute alcoholic liver injury was established on the 22 stday,Biochemical indicators of ocular blood in mice were observed.We also observed the change of liver morphology. RESULTS Under optimum conditions,we can obtain dropping pills having circular shape,touching with hardness and short dissolution time. Compared with the control group,the levels of alanine transaminase(ALT),glutamic-oxaloacetic transaminase(AST) and malondialdehyde(MDA) in model group were obviously increased(P<0.01),While the activity of Superoxide dismutase(SOD) were decreased. In addition,In model group,mice liver disorders,hepatic lobule fusion,accompanying a large number of patchy sample liver cell vacuoles,various sizes of fat vacuoles appeared in cytoplasm and inflammatory cell infiltration were visible around the central vein. On the contrary,compared with the model group,drug groups attenuated or even reversed hepatic pathological changes. Form gingerol dropping pill group,an increase in hepatic SOD activity and serum ALT and AST activities were found and a significant decrease in hepatic MDA content were also observed(P<0.01). CONCLUSION The prescription of gingerol dropping pills was reasonable,and the preparation process was simple. Gingerol dropping pills can protect liver from alcoholic liver injury to some extend,and the mechanism may be related to its antioxidant effect.
基金supported by National Natural Science Foundation of China(81673440 and 81473585)
文摘OBJECTIVE To investigate enhanced immune function of methionine encephalin(MENK)and its anti-tumor mechanism in CT26 colon cancer mouse model.METHODS 3×10~6CT26 cells were implanted subcutaneously in BALB/c mice.Four days after,MENK was peritoneally administrated at the concentration of 20 mg·kg^(-1) for 14 d.The percentage of MDSCs in bone marrow,spleen,blood,tumor and liver were detected by flow cytometry.Non-esterified fatty acid(NEFA),triglycerides(TG)and total cholesterol(T-CHO)in liver homogenate were tested by a NEFA test kit,a TG test kit and a T-CHO test kit respectively.qRT-PCR and Western blot were used to measure m RNA and protein levels of inflammation-,glycometabolsim-and lipometabolsim-associated indexes in liver.RESULTS MENK decreased percentages of MDSCs in bone marrow,spleen,blood and tumor in colon cancer mice.MENK-treated mice displayed elevated ratio of CD4^+T and CD8^+T cells in spleen as well as increased T and B lymphocytes proliferation.Meanwhile,MENK also ameliorated liver damage reflected by lower levels of GPT and GOT in serum and reduced risks of cancer-associated index including inflammation,high lipid and high glucose.Furthermore,MENK lowered down the levels of NEFA,TG and T-CHO in liver homogenate.MENK treatment decreased expression of p-STAT3,increased expression of p-AKT,IRS1 and Glut4 at protein level as well as reduced lipogenesis-associated genes and elevated glycolysis-associated genes in liver of tumor bearing mice.Also,abated expression of genes associated with MDSCs generation(M-CSF,GM-CSF,IL-6,IL^(-1)β)and migration(S100A9,KC)was observed within shrunken subcutaneous tumor by MENK intervention.CONCLUSION MENK has the ability to strength immune function against colon cancer by reducing MDSCs and improving liver metabolism.
基金Supported by National Natural Science Funds (30300259)
文摘Fatty liver in dairy cows, which is associated with decreased metabolic function of the liver, develops during times of elevated non-esterified fatty acid （NEFA） concentrations in the blood when the hepatic uptake of lipids exceeds the oxidation and secretion of lipids by the liver and then it will cause hepatic accumulation of triglyceride （TG）. The condition is often related to decreased health status, well-being, productivity, and reproductive performance of cows. Prevention of fatty liver in the transition period is always better than any treatments. The nutritional preventative strategies mainly focus either on decreasing the supply of NEFA to liver, and it aims to improve liver function or optimize the capacity then to dispose of NEFA by exporting them as triglycerides in lipoproteins （VLDL）. Good dry cow nutritional programs, combined with excellent feeding management to achieve high levels of dry matter intake throughout the transition period should be the first priority for management. Several different compounds can promote these metabolic actions. The addition of glucose precursors such as glycerol, propyelene glycol, or propionate salts to the feed in the transition diet can modify metabolism in a manner to decrease fatty acid mobilization from adipose tissue and reduce the likelihood of liver TG accumulation. Supplying some other specific nutrients to dairy cows during the transition period may increase rates of NEFA disposal, with resulting effects on performance, though the hepatic capacities for export as triglycerides within VLDL are relatively limited in ruminants. Further studies examining nutritional and management strategies are required to develop new preventive or treatment options that are more practical to reduce the occurrence of fatty liver and its adverse metabolic effects.
文摘Aim Liver fibrosis is a consequence of chronic liver disease which can progress into liver cirrhosis evenhepatocarcinoma. FuzhengHuayu （FZHY） , a Chinese herbal formula, had been reported to have the effect of anti- fibrosis. This study aims to investigate the effective targets and the mechanisms of FZHY on liver fibrosis. Methods The liver tissue samples of normal group, model group and FZHY-treated group were examined by microarray and iTRAQ. Profiles of differentially expressed genes （DEGs） and differentially expressed proteins （DEPs） in CC14-in- duced liver fibrosis model in rat were analyzed. GO and Pathway were analyzed by DAVID, and protein-protein in- teraction （PPI） was analyzed by STRING and cytoscape. The targets of FZHY compounds were predicted by TCM- SP. Results The results showed that 255 genes （ fold change ≥ 1.5, P 〈 0.05） and 507 proteins （ fold change ≥ 1.2 ,P 〈 0.05 ） were differentially expressed between FZHY group and model group. The high-throughput data of transcriptomics and proteomics was analyzed synthetically. DAVID function annotation analysis showed that these DEGS and DEPs both enriched in 15 GO terms, among drug metabolic process, response to extracellular stimulus, response to vitamin, arachidonic acid metabolic process, response to wounding and oxidation reduction may involve in liver fibrosis. KEGG pathway analysis showed that these DEGS and DEPs both enriched in 9 pathways, among arachidonic acid metabolism, retinol metabolism, metabolism of xenobiotics by cytochrome P450 and drug metabo- lism may be related to liver fibrosis. PPI analysis found that 10 overlapped core genes and proteins, among, Ugt2a3, Cyp2bl and Cyp3al8 were of higher degree, which are all enriched in retinol metabolism. Interestedly, Cyp2bl and Cyp3al8 were also predicted with TCMSP as the targets of FZHY compounds. Conclusion The re- sults indicated that the effective mechanism of FZHY against liver fibrosis is involved in the regulation of multiple targets and multiple pathways, among, retinol metabolism pathway by targeting Ugt2a3, Cyp2bl and Cyp3al8 may play an important role in the treatment of liver fibrosis.
文摘Nicotinic acid (N.C.)and choline were given orally to the periparturient cows to treat and prevent fatty liver.Blood parameters of glucose,β-hydroxybutyrate,albumin,total protein,magnesium,aspartate aminotransferase(AST)and non-esterified fatty acid (NEFA)weremeasured.There were no significant differences betWeen the treated and untreated groups in theplasma concentrations of albumin,total, protein and magnesium.Significant decrease in plasmaconcentrations of β-hydroxybutyrate,NEFA and AST were observed in the treated cows followiug administration of N.C.and choline.All the fatty liver cows(100% )treated with N.C.andcholine recovered within 5 weeks after calving compared with 71.4%(5/7) of untreated cows recovered.The incident rate of fatty liver postpartum in the cows with N.C.and cholinc given 2 weeksbefore calving was 30%(3/10),and the affected cows had a range of mild to moderate fatty liverwhilst the incident rate was 50% (5/10)in the untreated cows,which had a range of mild to ofsevere fatty liver.Meanwhile,the treated cows had a significant higher prodection of milk and shorter intervals from calving to uterine involution, to the first postpartum ovulation and to conception.
基金Supported by the National Natural Science Foundation of China (31172375)
文摘Effects of subchronic aluminum （Al） exposure on the function of rat liver were investigated in this experiment. A total of 48 male Wistar rats （4 weeks old） were randomly divided into four groups： experimental groups were orally exposed to 64.18, 128.36, 256.72 mg. kg^-1 body weight aluminum trichloride （AlCl3） in drinking water, and the control group with distilled water. The experiment lasted for 120 days. The activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-PX）, the concentration of malondialdehyde （MDA） in serum and liver, and alanine transarninase （ALT） and aspartate aminotransferase （AST） activities in serum were detected in all groups. The results showed that the activities of ALT, AST in serum and the concentrations of MDA in liver in the Al-treated groups significantly increased compared with the control group; the activities of GSH-PX and SOD in high-dose Al-treated group were significantly lower than those in control group. Our findings indicated that subchronic AI exposure could result in injures of lipid peroxidation and function in liver.
文摘Nonalcoholic fatty liver disease （NAFLD） is one of the common chronic liver disease, and may turn to cirrhosis of the liver or liver cancer, but its pathogenesis is unclear. Acanthoic acid （AA） have some improvement on drug-induced liver fibrosis, but its protective effect on Lieber-DeCarli （LD） liquid type fat diet-induced liver cell damage had less been reported, this study was conducted to determine whether acanthoic acid （AA） would a- meliorate LD-stimulated fatty liver in mice. Male C57BL/6 mice were randomly divided into six groups, including normal group, AA （40 mg · kg^-1） single group, LD-treated group, AA （20 mg· kg-1） plus LD-treated group, and AA （40 mg · kg^-1） plus LD-treated group and protive control group, they were given LD （20mL/only） , at same time gavage administration AA （20 mg · kg^-1, 40 mg· kg^-1） , while normal group were given normal diet. After 8 weeks, weighed again, then took blood by removalling eyeball, took liver. The serum aspartate aminotrans- ferase （AST）, alanine aminotransferase （ALT）, triglyceride （TG） and high density lipoprotein cholesterol （HDL- （i） in serum were determined with reagent strips. The liver was used to do Western blot, Hematoxylin ＆Eosin （H＆E） staining and Oil red staining. The Reagent results showed that administration of AA significantly inhibit the increase of AST, ALT caused by NAFLD, as well as TG and HDL-C in serum. Supplement of AA prevented LD-in- duced acidophilic necrosis, increased hepatocyte muclei and stromal inflammation infiltration as indicated by liver histopathological studies. The results indicated that AA significantly decreased the expression of SREBP-1, oL- TIMP1 and MMP-13 kept a dynamic equilibrium, TIMP1 was decreased, SMA, collagen-I, NF-KB. In addittion, while the expression of MMP-13 was increased. H＆Estaing and oil staing indicated that model group showed typical fatty degeneration, while the fatty liver histopathology of administration group showed significant improvement. These effects were associated with the down-regulation of SREBP-1 and particularly the activation of AMPK. All of these findings demostrated that AA had some improvement on LD-induced NAFLD, and its mechanism may be re- lated to SREBP1 and AMPK pathway.
