Attenuation of Oxidative Stress and Hepatotoxicity Induced By D–Galactosamine by a Polyherbal Formulation Ambrex–in vivo and in vitro Studies

Abstract:

Objective: To evaluate the hepatoprotective effect of Ambrex, a polyherbal formulation against D–galactosamine (D-GLN) induced hepatotoxicity in Swiss albino mice as well as in Chang liver cell lines. Materials and Methods: Ambrex was orally administered for a period of 7 days at dose levels of 250 and 500 mg/kg b.wt. D-GLN (250 mg/kg b.wt, i.p) was administered 24h prior to sacrifice the animals. The protective effect of Ambrex was evaluated by measuring plasma levels of aspartate transaminase (SGOT), alanine transaminase (SGPT), alkaline phosphatase (ALP), γ–glutamyltransferase (γGT) and total bilirubin. Its effect on antioxidants such as superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) and lipid peroxide(LPO) was also determined. Histopathological evaluation of liver tissues was carried out. Results: Data revealed that Ambrex was able to restore the levels of antioxidants such as SOD, Catalase, and Glutathione to near normal and reduced the elevated plasma levels of SGOT, SGPT, ALP, γ – GT and total bilirubin. It also inhibited the formation of hepatic malondialdehyde induced by D - GLN. In vitro studies revealed that Ambrex protected D- GLN induced hepatotoxicity (30μM/ ml) at dose levels of 5, 50 and 500ng/ml. Further, mRNA expression also illustrated that Ambrex inhibited the over expression of Bax, Caspase 3, TNF–α, IL–2 and CYP–450. A substantial decrease in the mRNA expression of anti-apoptotic marker Bcl2 was also observed. Conclusion: Results suggest that Ambrex has appreciable hepatoprotective effect which was evident from both in vivo and in vitro results.

Key words: Ambrex, D- Galactosamine, Hepatotoxicity, Chang Cells, Antioxidants.