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

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...

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Main Authors: Andrea J. Moreira, Graziella Rodrigues, Silvia Bona, Carlos Thadeu Cerski, Claudio A. Marroni, Jose L. Mauriz, Javier González-Gallego, Norma P. Marroni
Format: Article
Language:English
Published: Elsevier 2015-01-01
Series:Toxicology Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2214750014001504
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author Andrea J. Moreira
Graziella Rodrigues
Silvia Bona
Carlos Thadeu Cerski
Claudio A. Marroni
Jose L. Mauriz
Javier González-Gallego
Norma P. Marroni
author_facet Andrea J. Moreira
Graziella Rodrigues
Silvia Bona
Carlos Thadeu Cerski
Claudio A. Marroni
Jose L. Mauriz
Javier González-Gallego
Norma P. Marroni
author_sort Andrea J. Moreira
collection DOAJ
description 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.
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spelling doaj.art-d4206966b75249eeb770a72cf7db53062022-12-22T01:19:42ZengElsevierToxicology Reports2214-75002015-01-012C33334010.1016/j.toxrep.2014.11.015Oxidative stress and cell damage in a model of precancerous lesions and advanced hepatocellular carcinoma in ratsAndrea J. Moreira0Graziella Rodrigues1Silvia Bona2Carlos Thadeu Cerski3Claudio A. Marroni4Jose L. Mauriz5Javier González-Gallego6Norma P. Marroni7Center of Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, BrazilCenter of Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, BrazilCenter of Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, BrazilCenter of Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, BrazilCenter of Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, BrazilCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) and Institute of Biomedicine (IBIOMED), University of León, León, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) and Institute of Biomedicine (IBIOMED), University of León, León, SpainCenter of Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, BrazilHepatocellular 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.http://www.sciencedirect.com/science/article/pii/S2214750014001504HepatocarcinomaDiethylnitrosamineOxidative stressNuclear factor erythroid 2-related factor 2Nitric oxide synthaseHeat shock protein
spellingShingle Andrea J. Moreira
Graziella Rodrigues
Silvia Bona
Carlos Thadeu Cerski
Claudio A. Marroni
Jose L. Mauriz
Javier González-Gallego
Norma P. Marroni
Oxidative stress and cell damage in a model of precancerous lesions and advanced hepatocellular carcinoma in rats
Toxicology Reports
Hepatocarcinoma
Diethylnitrosamine
Oxidative stress
Nuclear factor erythroid 2-related factor 2
Nitric oxide synthase
Heat shock protein
title Oxidative stress and cell damage in a model of precancerous lesions and advanced hepatocellular carcinoma in rats
title_full Oxidative stress and cell damage in a model of precancerous lesions and advanced hepatocellular carcinoma in rats
title_fullStr Oxidative stress and cell damage in a model of precancerous lesions and advanced hepatocellular carcinoma in rats
title_full_unstemmed Oxidative stress and cell damage in a model of precancerous lesions and advanced hepatocellular carcinoma in rats
title_short Oxidative stress and cell damage in a model of precancerous lesions and advanced hepatocellular carcinoma in rats
title_sort oxidative stress and cell damage in a model of precancerous lesions and advanced hepatocellular carcinoma in rats
topic Hepatocarcinoma
Diethylnitrosamine
Oxidative stress
Nuclear factor erythroid 2-related factor 2
Nitric oxide synthase
Heat shock protein
url http://www.sciencedirect.com/science/article/pii/S2214750014001504
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