2-Hydroxy-4-methoxy benzoic acid attenuates the carbon tetra chloride-induced hepatotoxicity and its lipid abnormalities in rats via anti-inflammatory and antioxidant mechanism.

Abstract

Liver inflammation stimulates various inflammatory cytokines and initiates injury through oxidative stress. The aim of this study was to curtaile the liver injury through natural principles such as 2-hydroxy-4-methoxy benzoic acid (HMBA). The current study examines the hepatoprotective and lipid lowering effect of HMBA against carbon tetra chloride (CCl4)-mediated liver toxicity in male Wistar rats. The hepatoprotective effects of HMBA against CCl4-induced liver damage, were evident from low serum transaminases activities, reduced hepatic lipid peroxidation and collagen content, restoration of total glutathione, and recouping of the inflammatory cytokines, such as TNF-α, IL-1β, IL-10, and IL-6 levels. Further it was found that the treatment of HMBA, significantly lowered (P<0.01) the levels of total cholesterol, triglycerides, free fatty acids and phospholipids in serum and liver. To investigate the mechanism behind the hepatoprotective and lipid lowering effect, the activities of heme oxygenase (HO1), and myeloperoxidase (MPO) were measured and expression levels were quantified through western blot following HMBA administration. The results showed that HMBA administration significantly decreased the activity of HO1 (P<0.001), and increased the activity of MPO (P<0.001); further similar finding was observed in western analysis. The hepatoprotective, lipid lowering and shifting key defensive enzyme activities are similar to that of standard drug such as N-acetylcysteine. HMBA is competent of shielding liver from CCl4-induced hepatotoxicity, and this is associated with the lipid lowering, inflammatory cytokine restoration and induction of defensive enzyme activities.