Studies On Protective Effect Of Rhaponticum Uniforum On Mice With Acute Liver Injury By Apap

Objective:To study on the protective effect of Rhaponticum uniforum ethanol extract (RUEE) in acute injury of the mice liver by APAP.Methods:RUEE was administered intragastrically once daily for a period of 7 days. One hour after the final treatment, mice were treated intraperitoneally with 150mg/kg of APAP. Male mice were randomly divided into six groups of nine each. While the first group was maintained as normal control, groups of the model, RUEE and silymarin were administered 150mg/kg APAP (model),50 mg/kg RUEE plus APAP,100 mg/kg RUEE plus APAP,200 mg/kg RUEE plus APAP, and 100 mg/kg silymarin plus APAP, respectively. The serum alanin aminotransferase (ALT) and aspartate aminotransferase (AST), liver oxidative stress and antioxidative defense system were assayed by the colorimetric method.The hepatic proinflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), heme oxygenase-1 (HO-1), as well as the apoptotic-related B-cell leukemia/lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were determined with the western blot method. The liver homogenate malondialdehyde (MDA) and glutathione (GSH) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined by the colorimetric method.Result:1. The morphological observation revealed that RUEE attenuated the histopathological changes of liver sections induced by APAP in mice.2. APAP-induced hepatotoxicity was manifested by increased levels of serum marker enzymes and hepatic lipid peroxidation, and by decreased potential of hepatic antioxidative defense system. The administration of RUEE to APAP-treated mice not only decreased the serum toxicity marker enzymes, but also reduced hepatic oxidative stress, combined with elevated GSH content and antioxidative enzyme activities in the liver tissues. The APAP challenge caused a marked increase in the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA), and propagated lipid peroxidation with a concomitant reduction of reduced glutathione (GSH) and antioxidative enzyme activities in the liver, combined with suppressed potential of hepatic antioxidative defense system including superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities.3. Preadministration of RUEE reversed the significant changes in serum toxicity markers, hepatic oxidative stress, xenobiotic metabolizing enzymes and proinflammatory mediators induced by APAP.Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), heme oxygenase-1 (HO-1), Bcl-2 associated X protein (Bax) were elevated and B-cell leukemia/lymphoma-2 (Bcl-2) were decreased following APAP treatment. RUEE treatment inhibited the formation of liver nitrite, reduced the over-expression of iNOS, COX-2, HO-1 and Bax proteins. However, the protein expression of Bcl-2 was further elevated by RUEE treatment.Conclusion:RUEE has protective effect on the acute liver injury mice induced by APAP, the mechanism may be related to the elevated antioxidant capacity, suppressed inflammatory reaction, and inhibition of apoptosis of liver cell.