Toxicol Rep. 2014 Nov 28;2:333-340. doi: 10.1016/j.toxrep.2014.11.015. eCollection 2015.
Oxidative stress and cell damage in a model of precancerous lesions and advanced hepatocellular carcinoma in rats.
Toxicology reports
Andrea J Moreira, Graziella Rodrigues, Silvia Bona, Carlos Thadeu Cerski, Claudio A Marroni, Jose L Mauriz, Javier González-Gallego, Norma P Marroni
Affiliations
Affiliations
- Center of Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
- Graduate Program in Biological Sciences: Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
- Graduate Program in Medical Sciences: Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
- Department of Pathology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
- Graduate Program in Liver Diseases, Universidade Federal de Ciências da Saúde 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.
- Graduate Program in Cell and Molecular Biology Applied to Health, Universidade Luterana do Brasil, Canoas, RS, Brazil.
PMID: 28962366
PMCID: PMC5598147 DOI: 10.1016/j.toxrep.2014.11.015
Abstract
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.
Keywords: 2-AAF, 2-acetylaminofluorene; ALT, alanine aminotransferase; AP, alkaline phosphatase; AST, aspartate aminotransferase; DEN, diethylnitrosamine; Diethylnitrosamine; EDTA, ethylenediamine tetraacetic acid; GGT, gamma-glutamyl transferase; HCC, hepatocellular carcinoma; HSC, hepatic stellate cells; HSP70, heat shock 70-kDa protein; Heat shock protein; Hepatocarcinoma; Keap1, kelch-like ECH-associated protein 1; MDA, malonaldehyde; NO, nitric oxide; NQO1, NADPH quinone oxireductase-1; Nitric oxide synthase; Nrf2, nuclear factor erythroid 2-related factor 2; Nuclear factor erythroid 2-related factor 2; Oxidative stress; PVDF, polyvinylidene fluoride; SOD, superoxide dismutase; TBARS, thiobarbituric acid reactant substances; TGF-1β, transforming growth fator-1 beta; TTBS, Tris-buffered containing 0.05% Tween 20; UV, ultra violet; eNOS, endothelial nitric oxide synthase; iNOS, inducible nitric oxide synthase
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