Protective effects of 5-methoxypsoralen against acetaminophen-induced hepatotoxicity in mice

摘要

AIM:To investigate the hepatic protective effects of 5-methoxypsoralen(5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.METHODS:C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5,25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen(APAP) subcutaneously at a dose of 500 mg/kg.The 5-MOP alone group was treated with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP.Twenty-four hours after APAP administration,blood samples of mice were analyzed for serum enzyme alanine transaminase(ALT),aspartate transaminase(AST),lactate dehydrogenase(LDH) levels,and malondialdehyde(MDA),reduced glutathione(GSH) and oxidized glutathione(GSSG) of liver tissues were measured and histopathologic changes of the liver were observed.RESULTS:Compared with the vehicle control group,the serum levels(IU/L) of ALT,AST and LDH were all increased significantly in APAP group(8355 ± 3940 vs 30 ± 21,P 0.05;0.59 ± 0.07 vs 2.15 ± 1.07,P 0.05;5.330 ± 0.421 vs 3.306 ± 0.282,P < 0.05;6.180 ± 0.212 vs 3.306 ± 0.282,P < 0.05).In the group treated with 5-MOP but without APAP,the serum enzyme levels,the liver histopathologic manifestation,and the values of MDA and GSH/GSSG ratio were all normal.CONCLUSION:5-MOP can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity and possesses an antioxidative activity,and does not cause liver injury at the protective doses.