title: Inhibition of NF-κB activation by diethylcarbamazine prevents alcohol-induced liver injury in C57BL/6 mice.
abstract: Induction of NF-κB-mediated gene expression has been identified in the pathogenesis of alcoholic liver disease (ALD). Diethylcarbamazine (DEC) is a piperazine derivative drug with anti-inflammatory properties. The present study was designed to evaluate the effect of DEC on NF-κB pathways in mice undergoing alcoholism induced hepatic inflammation. Forty male C57BL/6 mice were divided equally into four groups: control group (C); DEC-treated group, which received 50mg/kg (DEC50); alcoholic group (EtOH), submitted to chronic alcohol consumption and the alcohol-DEC treated group (EtOH50), submitted to chronic alcoholism consumption plus DEC treatment. Histological analysis of the alcoholic group showed evident hepatocellular damage which was reduced in EtOH50 group. Immunohistochemistry and western blot results showed elevated expression of inflammatory markers such as MDA, TNF-α, IL-1β, COX-2 and iNOS in hepatocytes of EtOH group. However, low immunopositivity for these markers was detected following DEC treatment. In the EtOH group the activation of NF-κB was observed by an increase in the expression of both NF-κB and pNF-κB in hepatocytes. This expression was significantly reduced in livers of EtOH50 group. Protein expression of Iκβα was measured to determine whether activation of NF-κB might be the result of Iκβα degradation. It was observed that expression of this protein was low in EtOH group, while animals treated with DEC had a high expression of Iκβα. The results of the present study indicate that DEC alleviates alcoholic liver injury, in part by the inhibiting activation of NF-κB and by suppressing the induction of NF-κB-dependent genes.
authors: Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, PE, Brazil. Electronic address: silvabrunasantos@hotmail.com.
authors: Bruna Santos
authors: BS
authors: da Silva
authors: Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, PE, Brazil.
authors: Gabriel Barros
authors: GB
authors: Rodrigues
authors: Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, PE, Brazil.
authors: Sura Wanessa Santos
authors: SW
authors: Rocha
authors: Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, PE, Brazil.
authors: Edlene Lima
authors: EL
authors: Ribeiro
authors: Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, PE, Brazil.
authors: Fabiana Oliveira Dos Santos
authors: FO
authors: Gomes
authors: Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, PE, Brazil.
authors: Amanda Karolina Soares
authors: AK
authors: E Silva
authors: Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, PE, Brazil.
authors: Christina Alves
authors: CA
authors: Peixoto
mesh_terms: D000437:Alcoholism / Q000150:complications; D000818:Animals; D015153:Blotting, Western; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D004049:Diethylcarbamazine / Q000494:pharmacology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*
chemical_list: D016859:Lipoxygenase Inhibitors; D016328:NF-kappa B; D004049:Diethylcarbamazine
keywords: Alcoholism; Diethylcarbamazine; Hepatic injury; Inflammatory markers; NF-κB; Transcription factors