Evaluation of antioxidant and hepatoprotective effect of syringic acid against sodium valproate induced hepatotoxicity in Wistar rats and its anti cancer effect against HepG2 cells

Abstract

In the scenario of anti- epileptics contributing to 11% of the drug induced liver injury cases newlineand a paucity of literature related to the therapeutic use of anti- hepatotoxic drugs in Sodium newlinevalproate induced hepatotoxicity, an attempt was made to elucidate the same with a select plant newlinederived phenolic derivate Syringic Acid. The aim of this study was to evaluate the newlinehepatoprotective properties of concurrent administration and post-treatment of syringic newlineacid(SA) against sodium valproate-induced hepatotoxicity in rats. Further, drug induced liver newlineinjury over a long period can develop into hepatocellular carcinoma. The currently available newlinepharmacological treatment options for liver diseases such as CLD, cirrhosis and hepatocellular newlinecarcinoma are limited, expensive and largely ineffective. Therefore, this study also investigates newlinethe anticancer potential of syringic acid (SA) against hepG2 cells, a human hepatocellular newlinecarcinoma cell line. newlineMaterials and methods: The study was split into three phases, phase I concentrating on the newlinedocking affinity of SA with various key components of the inflammatory cascade. Phase II newlineinvestigated the anti- hepatotoxic effect of SA in concurrent administration of SA with Sodium newlinevalproate in a rat model. The anti- hepatotoxic effect of SA was also evaluated in a post newlinetreatment model using Sodium valproate. Phase III analysed the cytotoxic effect of SA in Hep newlineG2 cancer cell line. newlineResults: newlineThe docking study revealed that Syringic Acid strongly interacts with TNF-and#945; revealing newlinestrongest interaction with 6 hydrogen bonds. NF-and#954;B binds with syringic acid with very tight newlineinteraction and strong specificity. Syringic acid binds to the Iand#954;B at the Iand#954;B bindingsite with newlinevery close bonds and good bond strength. It also binds to p50 and p65 with strong bonds. SA newlinehas a definite interaction with the components of the inflammatory cascade thus proving its newlinepotential as an anti- inflammatory therapeutic agent to be of use in inflammatory pathologies. newline