title: Diethylnitrosamine-induced cirrhosis in Wistar rats: an experimental feasibility study.
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.
authors.affiliation: Postgraduate Program in Medical Sciences: Medicine, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2400, Porto Alegre, RS, Brazil.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bona
authors.forename: Andrea Janz
authors.initials: AJ
authors.lastname: Moreira
authors.forename: Graziella Ramos
authors.initials: GR
authors.lastname: Rodrigues
authors.forename: Carlos Thadeu
authors.initials: CT
authors.lastname: Cerski
authors.forename: Themis Reverbel
authors.initials: TR
authors.lastname: da Silveira
authors.forename: Claudio Augusto
authors.initials: CA
authors.lastname: Marroni
authors.forename: Norma Possa
authors.initials: NP
authors.lastname: Marroni
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D004052:Diethylnitrosamine; D005240:Feasibility Studies; D015227:Lipid Peroxidation; D008103:Liver Cirrhosis / Q000201:enzymology / Q000473:pathology*; D008297:Male; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D000637:Transaminases / Q000378:metabolism
chemical_list: D004052:Diethylnitrosamine; D013482:Superoxide Dismutase; D000637:Transaminases