Saponins from Panax japonicus protect against alcohol-induced hepatic injury in mice by up-regulating the expression of GPX3, SOD1 and SOD3

Abstract

Aims: The purpose of this study was to investigate the possible mechanism(s) of saponins from Panax japonicus (SPJ) on alcohol-induced hepatic damage in mice. Methods: SPJ were identified by high performance liquid chromatography-evaporative light scattering detection-mass spectrometry (LC-ELSD-MS). Non-toxic concentrations of SPJ were assayed on alcohol-induced hepatic injury in male ICR mice and human hepatic cells. The protective effects were evaluated by biochemical values, histopathological observations and the relative gene expression. Results. In vitro, SPJ showed significant hydroxyl radical scavenging capacity. In vivo, SPJ (50 mg/kg) could rectify the pathological changes of aspartate transaminase, alanine transaminase, malondialdehyde, reduced glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) caused by alcohol metabolism to normal levels except for hepatic GSH and CAT. In hepatic cells, the results were in agreement with foregoing results determined in mice after pretreatment of SPJ (100 μg/ml). RT-PCR results showed that CAT, GPX and SOD mRNA decreased by alcohol metabolism were reversed, in which GPX3, SOD1 and SOD3 could return to a normal level, but CAT, GPX1 and SOD2mRNAwere still evidently lower than the control. Histopathological observations provided supportive evidence for biochemical analyses. Conclusions: SPJ plays an important role in the protection of the structure and function of hepatic mitochondria and karyon by directly scavenging reactive oxygen species/free radicals and up-regulating the expression of antioxidant enzymes (SOD, GPX and CAT), especially to GPX3, SOD1 and SOD3. © The Author 2010. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved.