Alteration of Hepatic Proinflammatory Cytokines is Involved in the Resveratrol-Mediated Chemoprevention of Chemically-Induced Hepatocarcinogenesis

Thomas      Mbimba; Prabha      Awale; Deepak      Bhatia; Werner      J. Geldenhuys; Altaf      S. Darvesh; Richard      T. Carroll; Anupam      Bishayee

Abstract

Hepatocellular carcinoma (HCC), one of the most common cancers in the world, is a leading cause of cancerrelated mortality. HCC develops most frequently in the background of oxidative stress and chronic hepatic inflammation due to viral infections, alcohol abuse as well as exposure to environmental and dietary carcinogens. As the prognosis of HCC is extremely poor and mostly unresponsive to current chemotherapeutic treatment regimens, novel preventive approaches like chemoprevention are urgently needed. We have recently found that resveratrol, a dietary polyphenol present in grapes, berries, peanuts as well as red wine, prevents diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats through suppression of inflammation and oxidative stress. As cytokines are considered to be important mediators of inflammation, the objective of the present study was to investigate the effects of resveratrol on hepatic cytokines during DENA-initiated hepatocarcinogenesis in rats. Liver samples were harvested from our previous study in which resveratrol (50, 100 and 300 mg/kg) was found to exert a chemopreventive action against rat liver tumorigenesis induced by DENA. The levels of proinflammatory cytokines, namely tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin- 6 (IL-6), were measured using enzyme-linked immunosorbent assays. The mRNA expression of these cytokines was studied by reverse transcriptase-polymerase chain reaction for comparison. Resveratrol treatment reversed the DENAinduced alteration of the level and expression of hepatic TNF-α, IL-1β and IL-6. From the current results in conjunction with our previous findings, it can be concluded that resveratrol-mediated chemoprevention of rat liver carcinogenesis is related to alteration of proinflammatory cytokines.

Keywords: Diethylnitrosamine, hepatocarcinogenesis, inflammation, IL-1, IL-6, liver, resveratrol, TNF-α, (HCC), polyphenol, interleukin-1, IL-1β