Article
Effect of diethylcarbamazine on chronic hepatic inflammation induced by alcohol in C57BL/6 mice
Registro en:
SANTOS ROCHA, S. W. et al. Effect of diethylcarbamazine on chronic hepatic inflammation induced by alcohol in C57BL/6 mice. European Journal of Pharmacology, v. 689, n. 1–3, p. 194–203, ago. 2012.
1879-0712
10.1016/j.ejphar.2012.05.044
Autor
Rocha, Sura Wanessa Santos
Silva, Bruna Santos
Gomes, Fabiana Oliveira dos Santos
Soares e Silva, Amanda Karolina
Raposo, Catarina
Barbosa, Karla Patrícia Sousa
Torres, Dilênia de Oliveira Cipriano
Santos, Ana Célia Oliveira dos
Peixoto, Christina Alves
Resumen
Este estudo foi financiado pela Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE), Centro de Pesquisas Aggeu Magalhães da Fundação Oswaldo Cruz em Recife, Brasil (CPqAM / FIOCRUZ), Centro de Tecnologia Estratégica no Nordeste (CETENE) e Instituto Nacional de Biologia Estrutural e Bioimagem (INBEB). Some pharmacological studies showed that diethylcarbamazine (DEC) interferes with the arachidonic acid metabolism, acting as an anti-inflammatory drug. The chronic alcohol consumption activates the hepatic inflammatory response associated to T-cell activation and overproduction of pro-inflammatory cytokines. The present work analyzed the anti-inflammatory effect of DEC on hepatic cells of alcoholic mice. Thirty-two male C57BL/6 mice were equally divided in the following groups: (a) control group (C), which received only water, (b) DEC-treated group, which received 50 mg/kg for 12 day (DEC50), (c) the alcoholic group (EtOH), submitted to only alcohol and (d) the alcohol-DEC treated group (EtOH50), submitted to alcohol plus DEC treatment after the induction of chronic alcoholism for 5 weeks. Biochemical analyses were performed and liver fragments were processed for light microscopy, transmission electron microscopy, immunohistochemical and western blot. The level of AST increased significantly in alcoholic group whereas a significant reduction of serum AST was detected in the EtOH50 group. Histological and ultrastructural analysis of alcoholic group showed evident hepatocellular damage, which was strikingly reduced in the alcoholic DEC-treated group. Immunohistochemistry results revealed highly expression of inflammatory markers as MDA, NF-κB, TNF-α, IL-6, VCAM and ICAM by the hepatic cells of the EtOH group; however no immunoreactivity for any of these cytokines was detected after DEC treatment. Western blot analyses showed increased MCP-1 and iNOS expression in EtOH group, which was significantly inhibited by DEC treatment. According to the present results, DEC can be a potential drug for the treatment of chronic inflammation induced by chronic alcoholism. 2050-01-01