BACKGROUND：Edaravone can alleviate brain injury and improve neurological functions and symptoms. This study aimed to investigate the effect of edaravone on the p38Mitogen-activated protein kinases/Caspase-3 （p38MAPK...BACKGROUND：Edaravone can alleviate brain injury and improve neurological functions and symptoms. This study aimed to investigate the effect of edaravone on the p38Mitogen-activated protein kinases/Caspase-3 （p38MAPK/Caspase-3） pathway after diffuse brain injury （DBI） in rats. METHODS： DBI models were established according to the description of Marmarou＇s method. A total of 250 rats were divided （random number） into four groups： control group （CG, n=45）, model group （MG, n=77）, low-dose edaravone group （n=67, dosage 5 mg/kg） and high-dose edaravone group （n=61, dosage 10 mg/kg）. After 1,6, 24, 48, and 72 hours after injury, brain tissues were collected. The changes of neuron morphous in the hippocampal region were observed through Nissl staining. The expression levels of phosphorylated p38MAPK and caspase-3 were detected by immunohistochemistry and Western blotting respectively. Learning and memory function were tested with Morris water maze from the 3rd to 7th day after injury. RESULTS： Some neurons had histopathologic changes of necrosis and apoptosis in the model group compared with the control group. The phosphorylated p38MAPK expressions increased at 1,6, 4, and 48 hours （P〈0.05）, but no significant difference was observed at 72 hours （0.54±0.19 vs. 0.40±0.14, P〉0.05）. Caspase-3 expressions increased at 6, 24, 48, and 72 hours respectively （P〈0.05）, but there was no significant difference at 1 hour （0.59±0.29 vs. 0.40±0.17, P〉0.05）. From the 3rd to 6th day during the Morris water maze test, the latency to find the platform was significantly prolonged （P〈0.05） and times of rats crossing the platform was decreased on the 7th day （2.28±1.18 vs. 8.20±1.52, P〈0.05）. The phosphorylated p38MAPK expressions decreased at 6, 24 and 48 hours respectively in the low dose edaravone group compared with the model group （P〈0.05）, whereas no significant difference was seen at 1 hour （1.66±0.80 vs. 1.85±0.86, P〉0.05）. Caspase-3 expression decreased at 6, 24, 48, and 72 hours （P〈0.05）. The latency to find the platform was significantly shortened （P〈0.05）, and times of rats crossing the platform increased （4.17±1.15 vs. 2.28±1.18, P〈0.05）. The above mentioned parameters changed more significantly in the high-dose edaravone group than in the low-dose edaravone group. CONCLUSION：Edaravone can alleviate brain tissue damage after DBI, inhibit p38MAP signal activation after early injury, reduce the expression of caspase-3, and promote the recovery of neurological function in the late period.展开更多
BACKGROUND:Edaravone(3-methyl-1-penyl-2-pyrazolin-5-one) is a potent free-radical scavenger and has the antioxidant ability to inhibit lipid peroxidation.The study aimed to examine the effect of edaravone on protectin...BACKGROUND:Edaravone(3-methyl-1-penyl-2-pyrazolin-5-one) is a potent free-radical scavenger and has the antioxidant ability to inhibit lipid peroxidation.The study aimed to examine the effect of edaravone on protecting the acute injury of human type II alveolar epithelial cells(A549cells) induced by paraquat(PQ) and the change of production of reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD).METHODS:A549 cells were cultured and divided into PQ group(group P),edaravone-treated group(group E) and normal control group(group C).The cells in group P were exposed to paraquat(600 umol/L),and the cells in group E were treated with edaravone(100 umol/L) additionally,and no drug intervention was given to the cells in group C.Real-time monitoring by LSCM was used to detect the cell response and the intracellular dynamic change of ROS level in A549 cells after administration of PQ and edaravone.And the levels of SOD and MDA were detected respectively by biochemistry colorimetry.Data were expressed as mean ± standard error of the mean.Statistical analysis was carried out with the soft SPSS 16.0.RESULTS:The concentration of intracellular ROS significantly increased when PQ was given to A549 cells.But after administration of edaravone,the concentration of intracellular ROS was decreased.Compared to the PQ group,the levels of SOD in the edaravone group were significantly increased while the levels of MDA were markedly decreased.CONCLUSIONS:Paraquat can increase the oxidative stress,and induce the lipid peroxidation of A549 cells.Edaravone has the effect to scavenge reactive oxygen species,and to protect against the PQ-induced lung toxicity.展开更多
文摘BACKGROUND：Edaravone can alleviate brain injury and improve neurological functions and symptoms. This study aimed to investigate the effect of edaravone on the p38Mitogen-activated protein kinases/Caspase-3 （p38MAPK/Caspase-3） pathway after diffuse brain injury （DBI） in rats. METHODS： DBI models were established according to the description of Marmarou＇s method. A total of 250 rats were divided （random number） into four groups： control group （CG, n=45）, model group （MG, n=77）, low-dose edaravone group （n=67, dosage 5 mg/kg） and high-dose edaravone group （n=61, dosage 10 mg/kg）. After 1,6, 24, 48, and 72 hours after injury, brain tissues were collected. The changes of neuron morphous in the hippocampal region were observed through Nissl staining. The expression levels of phosphorylated p38MAPK and caspase-3 were detected by immunohistochemistry and Western blotting respectively. Learning and memory function were tested with Morris water maze from the 3rd to 7th day after injury. RESULTS： Some neurons had histopathologic changes of necrosis and apoptosis in the model group compared with the control group. The phosphorylated p38MAPK expressions increased at 1,6, 4, and 48 hours （P〈0.05）, but no significant difference was observed at 72 hours （0.54±0.19 vs. 0.40±0.14, P〉0.05）. Caspase-3 expressions increased at 6, 24, 48, and 72 hours respectively （P〈0.05）, but there was no significant difference at 1 hour （0.59±0.29 vs. 0.40±0.17, P〉0.05）. From the 3rd to 6th day during the Morris water maze test, the latency to find the platform was significantly prolonged （P〈0.05） and times of rats crossing the platform was decreased on the 7th day （2.28±1.18 vs. 8.20±1.52, P〈0.05）. The phosphorylated p38MAPK expressions decreased at 6, 24 and 48 hours respectively in the low dose edaravone group compared with the model group （P〈0.05）, whereas no significant difference was seen at 1 hour （1.66±0.80 vs. 1.85±0.86, P〉0.05）. Caspase-3 expression decreased at 6, 24, 48, and 72 hours （P〈0.05）. The latency to find the platform was significantly shortened （P〈0.05）, and times of rats crossing the platform increased （4.17±1.15 vs. 2.28±1.18, P〈0.05）. The above mentioned parameters changed more significantly in the high-dose edaravone group than in the low-dose edaravone group. CONCLUSION：Edaravone can alleviate brain tissue damage after DBI, inhibit p38MAP signal activation after early injury, reduce the expression of caspase-3, and promote the recovery of neurological function in the late period.
基金supported by a grant form the Natural Science Foundation of China(Grant No.C030105)
文摘BACKGROUND:Edaravone(3-methyl-1-penyl-2-pyrazolin-5-one) is a potent free-radical scavenger and has the antioxidant ability to inhibit lipid peroxidation.The study aimed to examine the effect of edaravone on protecting the acute injury of human type II alveolar epithelial cells(A549cells) induced by paraquat(PQ) and the change of production of reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD).METHODS:A549 cells were cultured and divided into PQ group(group P),edaravone-treated group(group E) and normal control group(group C).The cells in group P were exposed to paraquat(600 umol/L),and the cells in group E were treated with edaravone(100 umol/L) additionally,and no drug intervention was given to the cells in group C.Real-time monitoring by LSCM was used to detect the cell response and the intracellular dynamic change of ROS level in A549 cells after administration of PQ and edaravone.And the levels of SOD and MDA were detected respectively by biochemistry colorimetry.Data were expressed as mean ± standard error of the mean.Statistical analysis was carried out with the soft SPSS 16.0.RESULTS:The concentration of intracellular ROS significantly increased when PQ was given to A549 cells.But after administration of edaravone,the concentration of intracellular ROS was decreased.Compared to the PQ group,the levels of SOD in the edaravone group were significantly increased while the levels of MDA were markedly decreased.CONCLUSIONS:Paraquat can increase the oxidative stress,and induce the lipid peroxidation of A549 cells.Edaravone has the effect to scavenge reactive oxygen species,and to protect against the PQ-induced lung toxicity.
