Oxidative stress and cell damage in a model of precancerouslesions and advanced hepatocellular carcinoma in rats

Abstract

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer deaths through-out the world. This study was aimed to analyze oxidative stress and cell damage in amultistage model of liver carcinogenesis induced by diethylnitrosamine (DEN) in rats.Male Wistar rats weighing 145–150 g were divided into three groups: control, precan-cerous lesions (PL) (which received 100 mg DEN once a week every 6 weeks up to 28weeks), and advanced HCC (50 mg DEN once/twice per week up to 19 weeks). Lipid per-oxidation (TBARS), superoxide dismutase (SOD) activity, and expression of transforminggrowth factor-1 beta (TGF)-1 , endothelial and inducible nitric oxide syntahese (eNOS,iNOS), NADPH quinone oxireductase (NQO)-1, nuclear factor erythroid 2-related factor(NrF)2, kelch-like ECH-associated protein (Keap)1 and heat shock protein (HSP)70 weremeasured. TBARS concentration was augmented in the PL and advanced HCC groups. SODactivity, TGF-1 and Nrf2 expression were higher in animals with precancerous lesions.In advanced HCC, expression of NQO1 and iNOS increased while there was a decrease inHPS70 expression. Data obtained provide evidence for the differential activation of pro-teins involved in oxidative stress and cell damage during progression of carcinogenesis inan animal model of HCC.