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Santos Rocha S.W.,Institute Aggeu Magalhaes FIOCRUZ | Oliveira Dos Santos A.C.,University of Pernambuco | Dos Santos Silva B.,Institute Aggeu Magalhaes FIOCRUZ | De Cipriano Torres D.O.,Institute Aggeu Magalhaes FIOCRUZ | And 5 more authors.
Journal of Food and Drug Analysis | Year: 2012

Even though diethylcarbamazine (DEC) is widely used in the treatment for filaricide, its pharmacological potential is little explored. Protein malnutrition is highly incident in many populations in developing and under-developed countries and some of these populations are affected by lymphatic filariasis. The objective of the present study was to analyze the DEC effect in the hepatocytes of malnourished mice. Forty-eight male C57BL/6 mice were separated into groups: a control group (C, D25 and D50) and a malnourished group (M, MD25 and MD50). After being induced to malnutrition, the mice were submitted to 12 days of treatment with DEC solutions in concentrations of 25 and 50 mg/kg which were orally administered. Biochemical analyses were performed and liver fragments were processed for light microscopy and transmission electron microscopy. For the enzymatic dosages, it was possible to observe a significant reduction in serum albumin in group M (2.52 ± 0.415 g/dL) when compared with the control group (C) (3.27 ± 0.427 g/dL) which received no treatment. The histological analysis of the M group showed evident hepatocellular damage. However, groups MD25 and MD50 returned to basal levels. Groups M, MD25 and MD50 presented a significant increase in alkaline phosphate when compared with the control group (C). Histological analysis of group M showed evident hepatic steatosis, which characterizes hepatocellular damage. Groups MD25 and MD50 showed a decrease in steatosis. An ultrastructural analysis of the hepatocytes in groups MD25 and MD50 confirmed a reduction of lipid droplets. It is possible that the DEC effects have contributed to the reduction of hepatic changes caused by malnutrition. Source

Rodrigues G.B.,Institute Aggeu Magalhaes FIOCRUZ | Rocha S.W.S.,Institute Aggeu Magalhaes FIOCRUZ | Santos L.A.M.dos.,Institute Aggeu Magalhaes FIOCRUZ | de Oliveira W.H.,Institute Aggeu Magalhaes FIOCRUZ | And 4 more authors.
Clinical and Experimental Pharmacology and Physiology | Year: 2015

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. © 2015 Wiley Publishing Asia Pty Ltd. Source

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