Aim To investigate the protective effects of gentiopicroside （GPS） on acute alcohol-induced fatty liver.Methods Mice were treated with ethanol （5 g · kg^-11 of body weight） by gavage every 12 h for a total of...Aim To investigate the protective effects of gentiopicroside （GPS） on acute alcohol-induced fatty liver.Methods Mice were treated with ethanol （5 g · kg^-11 of body weight） by gavage every 12 h for a total of three do- ses to induce acute fatty liver. GPS （40 or 80 mg · kg^-1 ） was garaged with ethanol simultaneously for three doses. Administration of GPS significantly prevented the increases of serum ALT and AST caused by ethanol, as well as se- rum and hepatic TG. Results GPS could significantly prevent ethanol-induced hepatic steatosis and necrosis by H＆E and Oil Red O staining. GPS also significantly inhibited lipogenic genes including sterol regulatory element binding transcription factor 1 （ SREBP-1 ）, fatty acid synthase （FASN） and acetyl-CoA carboxylase （ACC） in eth- anol-treated mice. Additionally, GPS possessed the ability to prevent ethanol-induced acute liver steatosis, possibly through inducing the phosphorylation of AMP-activated protein kinase （AMPK） and liver kinase B1 （LKB1）. Af- ter treatment with GPS, peroxisome proliferator-activated receptor eL （PPARoL） protein expression in mouse liver was recovered as that level of normal mice. Ethanol treatment evoked P2X7r and caspase-1 protein expression, while GPS significantly suppressed those protein expressions. GPS may be developed as a potential therapeutic can- didate for ethanol-induced hepatic steatosis and inflammation.展开更多
OBJECTIVE To investigate the mechanism underlying valproate(VPA)-induced hepatic hepatotoxicity.METHODS C57B/6J mice were given VPA at500 mg·kg-1·d-1by intragastric administration for 14 consecutive days,whi...OBJECTIVE To investigate the mechanism underlying valproate(VPA)-induced hepatic hepatotoxicity.METHODS C57B/6J mice were given VPA at500 mg·kg-1·d-1by intragastric administration for 14 consecutive days,while the control group received the same volume of physiologic saline by intragastric administration for same days.Mice were sacrificed 24 h after the last administration.Blood samples were collected for plasma biochemical assays.Liver was fixed in 10%neutral buffered formalin for histopathological analysis,and RNA extraction.mR NA for selected genes expression encoding proteins key to fatty acid synthesis,triglyceride synthesis,fatty acid oxidation,phosphatidylcholine synthesis,and lipid uptake were measured using quantitative real-time PCR.RESULTS We found that VPA treatment induced hepatic injury in mice as evidenced by increased ALP,ATP,ASP,GGT,and LDH.Histopathological analysis of the liver in mice treated with VPA showed increased microvesicular steatosis in cytoplasm.More importantly,VPA treatment increased the m RNA expressions of sterol regulatory element binding protein(SREBP)-1c,peroxisome proliferator-activated receptor(PPAR)γ,diacylgycerol acyltransferase(DGAT)2,and cluster of differentiation(CD)36,while the mR NA levels of stearoyl-Co A desaturase(SCD)1,DGAT1,liver X receptorsα(LXRα),carnitine palmitoyltransferase(CPT)1,malonyl coenzyme A decarboxylase(MCD),uncoupling protein(UCP)2,phosphatidylethanolamine N-methyltransferase(PEMT),and pregnenolone X receptor(PXR)displayed significant decrease.CONCLUSION Our data showed that VPA induced disruption of hepatic lipid homeostasis,which could be helpful for a better under-standing of the mechanism underlying VPA-induced hepatotoxicity and for a better use of VPA.展开更多
文摘Aim To investigate the protective effects of gentiopicroside （GPS） on acute alcohol-induced fatty liver.Methods Mice were treated with ethanol （5 g · kg^-11 of body weight） by gavage every 12 h for a total of three do- ses to induce acute fatty liver. GPS （40 or 80 mg · kg^-1 ） was garaged with ethanol simultaneously for three doses. Administration of GPS significantly prevented the increases of serum ALT and AST caused by ethanol, as well as se- rum and hepatic TG. Results GPS could significantly prevent ethanol-induced hepatic steatosis and necrosis by H＆E and Oil Red O staining. GPS also significantly inhibited lipogenic genes including sterol regulatory element binding transcription factor 1 （ SREBP-1 ）, fatty acid synthase （FASN） and acetyl-CoA carboxylase （ACC） in eth- anol-treated mice. Additionally, GPS possessed the ability to prevent ethanol-induced acute liver steatosis, possibly through inducing the phosphorylation of AMP-activated protein kinase （AMPK） and liver kinase B1 （LKB1）. Af- ter treatment with GPS, peroxisome proliferator-activated receptor eL （PPARoL） protein expression in mouse liver was recovered as that level of normal mice. Ethanol treatment evoked P2X7r and caspase-1 protein expression, while GPS significantly suppressed those protein expressions. GPS may be developed as a potential therapeutic can- didate for ethanol-induced hepatic steatosis and inflammation.
基金The project supported by National Natural Science Foundations of China(81573658,81102886)
文摘OBJECTIVE To investigate the mechanism underlying valproate(VPA)-induced hepatic hepatotoxicity.METHODS C57B/6J mice were given VPA at500 mg·kg-1·d-1by intragastric administration for 14 consecutive days,while the control group received the same volume of physiologic saline by intragastric administration for same days.Mice were sacrificed 24 h after the last administration.Blood samples were collected for plasma biochemical assays.Liver was fixed in 10%neutral buffered formalin for histopathological analysis,and RNA extraction.mR NA for selected genes expression encoding proteins key to fatty acid synthesis,triglyceride synthesis,fatty acid oxidation,phosphatidylcholine synthesis,and lipid uptake were measured using quantitative real-time PCR.RESULTS We found that VPA treatment induced hepatic injury in mice as evidenced by increased ALP,ATP,ASP,GGT,and LDH.Histopathological analysis of the liver in mice treated with VPA showed increased microvesicular steatosis in cytoplasm.More importantly,VPA treatment increased the m RNA expressions of sterol regulatory element binding protein(SREBP)-1c,peroxisome proliferator-activated receptor(PPAR)γ,diacylgycerol acyltransferase(DGAT)2,and cluster of differentiation(CD)36,while the mR NA levels of stearoyl-Co A desaturase(SCD)1,DGAT1,liver X receptorsα(LXRα),carnitine palmitoyltransferase(CPT)1,malonyl coenzyme A decarboxylase(MCD),uncoupling protein(UCP)2,phosphatidylethanolamine N-methyltransferase(PEMT),and pregnenolone X receptor(PXR)displayed significant decrease.CONCLUSION Our data showed that VPA induced disruption of hepatic lipid homeostasis,which could be helpful for a better under-standing of the mechanism underlying VPA-induced hepatotoxicity and for a better use of VPA.
