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Diethylnitrosamine-induced cirrhosis in Wistar rats: an experimental feasibility study

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Abstract

The experimental models of the development of cirrhosis in rats require a long time. Many studies in animals have demonstrated similarities in histological pattern with human cirrhosis. Just like the relation between cirrhosis and increased lipid peroxidation (LPO), which contributes to the worsening of the disease. However, few studies have focused on the reduction of time to establish cirrhosis and evaluated the expression of heat-shock protein 70 (HSP70) in cirrhotic livers of rodents. The present study proposes the adaptation of an experimental cirrhosis model using diethylnitrosamine (DEN). Twenty-six male Wistar rats, weighing ±270 g, divided into two groups: (i) CO-control and (ii) DEN-diethylnitrosamine. The DEN group received 50 mg/kg of DEN twice a week intraperitoneally for 7 weeks. The model developed cirrhosis in 7 weeks. The liver function tests showed that the animals with DEN-induced cirrhosis had increased levels when compared to control. The histological examination showed changes in the liver architecture, with severe ductal proliferation, signs of chronic damage, cholestasis, lymphocytic infiltrate, steatosis, and extensive parenchymal loss. We also found nodular formations with homogeneous pattern, increased LPO, increased expression of iNOS, TGF beta, α-SMA, and NQO1. However, the HSP70 expression was reduced in cirrhotic animals. This study showed signs of cirrhosis in liver based on biochemical, histological, and molecular analysis. The reduced expression of HSP70 appears to be associated with increased oxidative stress, contributing to the worsening of the disease.

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Acknowledgments

This study was supported by grants from the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundo de Incentivo à Pesquisa e Eventos (FIPE) of the Hospital de Clínicas of Porto Alegre (HCPA), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Laboratório Experimental de Hepatologia e Gastroenterologia (HCPA/UFRGS), and Laboratório de Estresse Oxidativo e Antioxidantes (ULBRA).

Conflict of interest

The authors of this article declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Postgraduate Program in Medical Sciences: Medicine, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2400, Porto Alegre, RS, Brazil

    Silvia Bona, Graziella Ramos Rodrigues & Norma Possa Marroni

  2. Center of Experimental Research, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2400, Porto Alegre, RS, Brazil

    Silvia Bona, Andrea Janz Moreira, Graziella Ramos Rodrigues, Themis Reverbel da Silveira & Norma Possa Marroni

  3. Postgraduate Program in Biological Sciences: Physiology, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS, Brazil

    Andrea Janz Moreira & Norma Possa Marroni

  4. Department of Pathology, School of Medicine, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2400, Porto Alegre, RS, Brazil

    Carlos Thadeu Cerski

  5. Postgraduate Program in Liver Diseases, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua Sarmento Leite, 245, Porto Alegre, Rio Grande do Sul, Brazil

    Claudio Augusto Marroni

  6. Postgraduate Program in Cell and Molecular Biology Applied to Health, Universidade Luterana do Brasil, Av. Farroupilha, 8001, Canoas, RS, Brazil

    Norma Possa Marroni

  7. Rua José Kanan Aranha, 102, Porto Alegre, RS, Brazil, CEP: 91760470

    Norma Possa Marroni

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  1. Silvia Bona
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Correspondence to Norma Possa Marroni.

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Bona, S., Moreira, A.J., Rodrigues, G.R. et al. Diethylnitrosamine-induced cirrhosis in Wistar rats: an experimental feasibility study. Protoplasma 252, 825–833 (2015). https://doi.org/10.1007/s00709-014-0719-8

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