Valproate Ameliorates Diethylnitrosamine/Phenobarbital- Induced Hepatic Cancer via the Role of TNF-α and TGF-β1

摘要

Background and Objective: Hepatocellular Carcinoma (HCC) constitutes approximately 90% of all primary cases of liver cancer and no appropriate management of pharmacological medications are currently available on the market for diagnosis or cure of this lethal disease. This study aimed to scrutinize the chemoprotective effect of valproate against diethylnitrosamine(DEN) induced HCC in rats. Materials and Methods: Single intraperitoneal injection of DEN (200 mg kgG1 ) was used for induction of the HCC and Phenobarbital (Pb) was used to boost the HCC and rats were treated with Doxorubicin (DOX) and valproate (1.25 and 2.5 mg kgG1 ). The rats were macroscopically examined and estimated the organ weight. Hepatic, biochemical, antioxidant, pro-inflammatory cytokines and inflammatory mediators were estimated. Results: Valproate considerably reduced the hepatic nodules and altered the organ weight as compared to DEN treated rats. valproate considerably reduced the level of "-fetoprotein and other hepatic enzymes (Alkaline Phosphates (ALP), Aspartate Aminotransferase (AST) and Alanine Transaminase (ALT)). Valproate significantly increased the level of total protein, albumin, globulin, A/G ratio and reduced the level of total bilirubin. Valproate considerably reduced the LPO level and boosted the Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), Glutathione (GSH), Catalase (CAT), Glutathione-S-Transferase (GST) level. Conclusion: Valproate reduced the cytokines such as TNF-", IL-6, IL-1$ and inflammatory mediator include NF-kB. Valproate significantly reduced the TGF-$1 level in hepatic tissue. The finding exhibited the therapeutic effect of valproate for hepatocellular carcinoma treatment.