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Diethylcarbamazine: Possible therapeutic alternative in the treatment of alcoholic liver disease in C57BL/6 mice
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
Affiliation:1. Ultrastructure Laboratory, Institute Aggeu Magalh?es ‐ FIOCRUZ, Recife, Brazil;2. Postgraduate Program in Biotechnology (RENORBIO), Federal University of Pernambuco, Pernambuco, Brazil
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.
Keywords:alcoholic liver disease  diethylcarbamazine  inflammation  NF‐κ  B
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