Resveratrol Normalizes Hyperammonemia Induced Pro-Inflammatory and Pro-Apoptotic Conditions in Rat Brain

Abstract

Chronic liver failure (CLF) led hyperammonemia (HA) is known to develop into a metabolic brain disorder known as hepatic encephalopathy (HE). TNF-α is now considered responsible for mounting neurological complications associated with HA/HE. However, the mechanism that connects inflammation and neuroexcitotoxicity is not yet clear. Resveratrol (RSV) is a natural antioxidant and known to mediate its therapeutic actions mainly by scavenging (ROS). RSV is predicted to modulate many cellular targets as well; however, there is little information on its neuroprotective roles. This article describes the effect of RSV treatment on the expression profiles of TNF-α, NFkB and apoptotic factors; Bcl2 & Bax in cerebral cortex and cerebellum of the CLF rats (induced by administration of 100 mg thioacetamide i.p. for 10 days) confirming moderate grade HA. A significant increase in mRNA level of TNF-α (p<0.001) in both of the rat brain regions of HA (cerebral cortex and cerebellum). This was consistent with a similar enhancement in the level of NFkB, a transcription factor for TNF-α synthesis, and thus, suggests induction TNF-α led inflammation in the brain during persistent HA. A significant decline in Bcl2 level (p<0.001) with a significantly enhanced level of Bax further suggested a neurodegenerative condition in those brain regions of the HA rats. Moreover, post treatment of those HA rats, with 10 mg/Kg b.w. RSV for a week, was found to bring all the factors towards their normal level in both the brain regions. The finding suggest that RSV is able to ameliorate moderate HA induced TNF-α led inflammatory cascade and proapoptotic neurodegenerative condition in the rat brain primarily by modulating expression of the inflammatory and apoptotic factors.