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: Gabriel Barros Rodrigues, Sura Wanessa Santos Rocha, Laise Aline Martins Dos Santos, Wilma Helena de Oliveira, Fabiana Oliveira Dos Santos Gomes, Maria Eduarda da Rocha de França, Deniele Bezerra Lós, Christina Alves Peixoto
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 42 Issue 4 Pg. 369-79 (Apr 2015) ISSN: 1440-1681 [Electronic] Australia
• PMID: 25676413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Wiley Publishing Asia Pty Ltd.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Inflammation Mediators
• Lipids
• NF-kappa B
• Transforming Growth Factor beta
• Collagen
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Ptgs2 protein, mouse
• Cyclooxygenase 2
• Aspartate Aminotransferases
• AMP-Activated Protein Kinases
• Diethylcarbamazine

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Aspartate Aminotransferases (blood)
• Collagen (metabolism)
• Cyclooxygenase 2 (genetics)
• Cytokines (metabolism)
• Cytoprotection
• Diethylcarbamazine (pharmacology)
• Inflammation Mediators (metabolism)
• Lipids (blood)
• Liver (drug effects, metabolism, pathology)
• Liver Cirrhosis, Alcoholic (drug therapy, metabolism, pathology)
• Male
• Mice, Inbred C57BL
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Signal Transduction (drug effects)
• Transforming Growth Factor beta (metabolism)