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

Toxicology Reports

Norma P. Marroni¹  Silvia Bona¹  Andrea J. Moreira¹  Carlos Thadeu Cerski¹  Graziella Rodrigues¹  Claudio A. Marroni¹  Javier González-Gallego²  Jose L. Mauriz² 

[1] Center of Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil;Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) and Institute of Biomedicine (IBIOMED), University of León, León, Spain;

关键词: Hepatocarcinoma;    Diethylnitrosamine;    Oxidative stress;    Nuclear factor erythroid 2-related factor 2;    Nitric oxide synthase;    Heat shock protein;   

DOI  :  10.1016/j.toxrep.2014.11.015

来源: DOAJ

【 摘 要 】

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer deaths throughout the world. This study was aimed to analyze oxidative stress and cell damage in a multistage model of liver carcinogenesis induced by diethylnitrosamine (DEN) in rats. Male Wistar rats weighing 145–150 g were divided into three groups: control, precancerous lesions (PL) (which received 100 mg DEN once a week every 6 weeks up to 28 weeks), and advanced HCC (50 mg DEN once/twice per week up to 19 weeks). Lipid peroxidation (TBARS), superoxide dismutase (SOD) activity, and expression of transforming growth factor-1 beta (TGF)-1β, 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 were measured. TBARS concentration was augmented in the PL and advanced HCC groups. SOD activity, TGF-1β and Nrf2 expression were higher in animals with precancerous lesions. In advanced HCC, expression of NQO1 and iNOS increased while there was a decrease in HPS70 expression. Data obtained provide evidence for the differential activation of proteins involved in oxidative stress and cell damage during progression of carcinogenesis in an animal model of HCC.

【 授权许可】

Unknown