Effect of diethylcarbamazine on chronic hepatic inflammation induced by alcohol in C57BL/6 mice.
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.
Departamento de Entomologia, Centro de Pesquisas Aggeu Magalhães, Av. Moraes Rego s/n, Cidade Universitária, Recife, PE 50670-420, Brazil. surawanessa@gmail.com
Sura Wanessa
SW
Santos Rocha
Bruna Santos
BS
Silva
Fabiana Oliveira  dos Santos
FO
Gomes
Amanda Karolina
AK
Soares e Silva
Catarina
C
Raposo
Karla Patrícia Sousa
KP
Barbosa
Dilênia de Oliveira Cipriano
Dde O
Torres
Ana Célia Oliveira
AC
dos Santos
Christina Alves
CA
Peixoto
D000818:Animals; D004049:Diethylcarbamazine / Q000494:pharmacology / Q000627:therapeutic use*; D000431:Ethanol / Q000008:administration & dosage* / Q000009:adverse effects; D006519:Hepatitis, Alcoholic / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016896:Treatment Outcome
D018836:Inflammation Mediators; D000431:Ethanol; D004049:Diethylcarbamazine