Daphnetin Ameliorates the Expansion of Chemically Induced Hepatocellular Carcinoma via Reduction of Inflammation and Oxidative Stress

Abstract

Hepatocellular carcinoma (HCC) is the 5th most common cancer disease and the 3rd cause of cancer related disease. Oxidative stress and inflammatory reactions are increases due to the expansion of hepatic cancer. Daphnetin is a well-known antioxidant and anti-inflammatory drug. The current experimental study was exploring the chemoprotective effect of daphnetin against diethylnitrosamine (DEN) induced HCC in rats and scrutinizing the possible mechanism. In this experimental study, Swiss Wistar rats were used for the current protocol and intraperitoneal injection of DEN (200 mg/kg) and phenobarbital (8 mg/kg) were used for the induction and progression of HCC and after induction the HCC, the rats were received the oral administration of different doses of daphnetin. Body weight was estimated at regular time intervals. Macroscopical evaluation was done at the end of the experimental study for the confirmation of hepatic nodules. Hepatic markers, antioxidant and inflammatory mediators were estimated in the serum of experimental rats. Daphnetin treatment successfully attenuated the hepatic injury induced by DEN/Pb as shown by the suppressed the levels of biochemical parameters including alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (T-Bil) and total protein (TP). Daphnetin significantly (p < 0.001) enhanced the level of glutathione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and decreased the malonaldehyde (MDA) level. Daphnetin treatment significantly altered the level of phase I and phase II enzymes and also significantly (p < 0.001) decreased the level of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α); inflammatory mediators include cyclooxygenase-2 (COX-2), nuclear kappa B factor (NF-κB) and prostaglandin (PGE2). Collectively, we can say that daphnetin suggestively suppressed the hepatic cancer via suppression of antioxidant and inflammatory reactions.