Abstract

Hepatic encephalopathy (HE) is a serious neuropsychiatric syndrome due to either acute or chronic hepatic failure. This study aimed to investigate the possible neuroprotective effect of chrysin, a natural flavenoid on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. HE was induced in Wistar rats by intraperitoneal (i.p.) injection of TAA (200?mg/kg) for three alternative days. Normal and control groups received the vehicle for 21 days. Chrysin was administered orally for 21 days (25, 50, 100?mg/kg) and starting from day 17, rats received i.p. dose of TAA (200?mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were conducted. Chrysin improved TAA-induced motor incoordination as it reduced final falling latency time in rotarod test, ameliorated cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes namely, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.