Neuromodulatory Role of L-arginine; Nitric Oxide Precursor Against Thioacetamide Induced-Hepatic Encephalopathy in Rats via Downregulation of Nrf-2/NF- κB -mediated Apoptosis

Abstract The goal of the current study was to investigate the impact of arginine (ARG); a NO precursor, on thioacetamide (TAA)-induced HE. To achieve this goal, rats received TAA (100 mg/kg, i.p) thrice weekly for six consecutive weeks to induce HE. TAA-injected rats were administered ARG (100 mg/kg/day; p.o.) concurrently with TAA for six consecutive weeks. Blood was then withdrawn and rats were sacrificed, liver and brain tissues were isolated. Results of the present study demonstrated that ARG administration to TAA-induced HE in rats revealed a restoration in the serum and brain ammonia levels as well as serum AST, ALT, ALP and T. bilirubin levels as well as behavioral alterations evidenced by restoration in locomotor activity, motor skill performance, and memory impairment. ARG showed also attenuation in hepatic and brain biochemical biomarkers, pro-inflammatory cytokines and oxidative stress biomarkers. All these results were confirmed by histopathological evaluation as well as ultra-structural image of the cerebellum using a transmission electron microscope. Furthermore, treatment with ARG exhibited ameliorated immunological reactivity of Nrf2 and cleaved caspase-3 proteins in cerebellum and hepatic tissue. From all the previous findings, it can be concluded that ARG showed a beneficial role in modulating the adverse complications associated with TAA-induced hepatic encephalopathy in rats via reducing hyperammonemia and downregulating ROS and Nrf-2/NF- κB -mediated apoptosis.