Andrographis paniculata Ameliorates Hyperammonemia Induced Oxidative Stress in Rat Brain by Activating Antioxidant Enzymes

Liver failure leads to hyperammonemia (HA), which trigger hepatic encephalopathy (HE), a neuropsychiatric syndrome. HA mediated oxidative stress in brain is believed to play crucial role in the pathogenesis of HE, present study was aimed to evaluate the therapeutic effect of Andrographis paniculata Nees aqueous extract (APAE) against acute and chronic HA induced oxidative stress in the rat cerebral cortex and cerebellum. Acute HA was induced by the administration of two intraperitoneal (i.p.) injections of ammonium acetate (AA), first with 10 x 10(3) mu mol/kg bw and 8 x 10(3) mu mol/kg bw at 30 min intervals; however, chronic HA was produced by a fixed dose of 10 x 10(3) mu mol/kg bw for 3 consecutive days. Therapeutic doses of APAE (250 mg/kg bw) were given orally. Oxidative stress markers, lipid peroxidation (LPO), total thiols (GSH), major antioxidant enzymes, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), and glutathione reductase (GR) were studied. In comparison to the control group, significantly increased levels of LPO but decreased GSH levels were accompanied by decreased levels of antioxidant enzymes SOD, catalase, GPX, and GR in both the cerebral cortex and cerebellum of rats with acute HA; however, in case of chronic HA, such patterns were found only in cerebellum while cerebral cortex showed adaptation against oxidative stress by activating antioxidant enzymes. The APAE treatment reversed situation of oxidative stress toward normal levels in both acute and chronic HA rats by activating the antioxidant enzymes and lowering the increased ammonia levels. Together these findings suggested that APAE could be an effective antioxidant treatment option for the HE patients suffering from HA induced oxidative stress in the brain tissues.