Syringic acid protects against thioacetamide-induced hepatic encephalopathy: Behavioral, biochemical, and molecular evidence

The objective of this study was to elucidate the effects of syringic acid on thioacetamide-induced hepatic encephalopathy which is a complex serious syndrome with neuropsychiatric abnormalities related to acute liver dysfunctions like cirrhosis. Rats were treated with syringic acid (50 and 100 mg/kg, p.o.) for 14 days in treatment groups. Hepatic encephalopathy was induced by three doses of (200 mg/kg i.p.) thioacetamide injection. Syringic acid effectively alleviated thioacetamide-induced hepatic injury via reduction in ammonia, AST, ALT, ALP, LDH and decrease in oxidative stress (decreased MDA, ROS and increased SOD and GSH). Syringic acid also attenuated inflammatory injury by suppressing TNF-alpha, IL-1 beta, and NF-kappa B and increasing IL-10. The caspase-3 expression was also down-regulated in both liver and brain tissues. Immunohistochemical results confirmed the recovery with syringic acid by downregulation of iNOS, 8-OHdG and GFAP expression. Syringic acid decreased the deteriorating effects of thioacetamide as seen by reduced ammonia concentration and also preserved astrocyte and hepatocyte structure. The behavioral test results from elevated plus maze test, similar to the open-field locomotor test results, confirmed that syringic acid can reverse behavioral impairments. In conclusion, syringic acid exerted hepatoprotective and neuroprotective effects against hepatic encephalopathy by mitigating hepatotoxicity biomarkers, exerting antioxidant, anti-inflammatory effects in addition to suppressing hyperammonemia.