title: Diethylcarbamazine: possible therapeutic alternative in the treatment of alcoholic liver disease in C57BL/6 mice.
abstract: Alcoholic liver disease is a major cause of chronic liver disease worldwide. Diethylcarbamazine (DEC) is a drug that has anti-inflammatory properties due to its effects on the metabolism of arachidonic acid. The present study examined the anti-inflammatory effects of DEC on the mechanisms of alcoholic liver disease. C57BL/6 mice were divided into seven groups: (i) control; (ii) DEC 50 mg/kg; (iii) alcohol; (iv) alcohol + DEC 50 mg/kg; (v) alcohol + celecoxib 50 mg/kg; (vi) alcohol + pyrrolidine dithiocarbamate 100 mg/kg; and (vii) alcohol + pyrrolidine dithiocarbamate 100 mg/kg + DEC 50 mg/kg. Liver fragments were stained with haemotoxylin-eosin and Sirius red, and processed for immunofluorescence, western blot, and immunohistochemistry. Serum was also collected for biochemical measurements. Alcohol induced liver damage, elevated collagen content, and increased expression of nuclear factor kappa-light-chain-enhancer of activated B cells and inflammatory markers (tumour necrosis factor-α, interferon-γ, interleukin-1β, inducible nitric oxide synthase, cyclooxygenases-2, and transforming growth factor-β). Treatment with DEC was able to reduce liver damage, collagen content, the expression of nuclear factor kappa-light-chain-enhancer of activated B cells and inflammatory markers; it also ameliorated biochemistry parameters (total cholesterol, high-density lipoprotein cholesterol, triglyceride content and aspartate aminotransferase) and increased the expression of anti-inflammatory markers (p-5' adenosine monophosphate-activated protein kinase and interleukin-10). Future clinical trials may demonstrate that oral administration of DEC may be suitable for the treatment of alcoholic liver disease and other liver diseases.
authors: Ultrastructure Laboratory, Institute Aggeu Magalhães - FIOCRUZ, Recife, Brazil.
authors: Gabriel Barros
authors: GB
authors: Rodrigues
authors: Sura Wanessa Santos
authors: SW
authors: Rocha
authors: Laise Aline Martins
authors: LA
authors: Dos Santos
authors: Wilma Helena
authors: WH
authors: de Oliveira
authors: Fabiana Oliveira Dos Santos
authors: FO
authors: Gomes
authors: Maria Eduarda da Rocha
authors: ME
authors: de França
authors: Deniele Bezerra
authors: DB
authors: Lós
authors: Christina Alves
authors: CA
authors: Peixoto
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D003094:Collagen / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection; D004049:Diethylcarbamazine / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008055:Lipids; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D003094:Collagen; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D001219:Aspartate Aminotransferases; D055372:AMP-Activated Protein Kinases; D004049:Diethylcarbamazine
keywords: NF-κB; alcoholic liver disease; diethylcarbamazine; inflammation