Ethanol consumption increases the expression of endothelial nitric oxide synthase, inducible nitric oxide synthase and metalloproteinases in the rat kidney

Autor(es)

Tirapelli, Luis F. ^[1] ; Martins-Oliveira, Alisson ^[1] ; Batalhao, Marcelo E. ^[2] ; Tirapelli, Daniela P. ^[1] ; Carnio, Evelin C. ^[2] ; Tanus-Santos, Jose E. ^[1] ; Queiroz, Regina H. ^[3] ; Padovan, Claudia M. ^[4] ; Tirapelli, Carlos R. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, BR-05508 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Coll Nursing Ribeirao Preto, BR-05508 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Clin Toxicol & Food Sci Anal, BR-05508 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeirao Preto, Dept Psychol, BR-05508 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Pharmacy and Pharmacology; v. 64, n. 1, p. 68-76, JAN 2012.
• Citações Web of Science: 9

Resumo

Objectives The effects of longterm ethanol consumption on the levels of nitric oxide (NO) and the expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS) and metalloproteinase-2 (MMP-2) were studied in rat kidney. Methods Male Wistar rats were treated with 20% ethanol (v/v) for 6 weeks. Nitrite and nitrate generation was measured by chemiluminescence. Protein and mRNA levels of eNOS and iNOS were assessed by immunohistochemistry and quantitative real-time polymerase chain reaction, respectively. MMP-2 activity was determined by gelatin zymography. Histopathological changes in kidneys and indices of renal function (creatinine and urea) and tissue injury (mitochondrial respiration) were also investigated. Results Chronic ethanol consumption did not alter malondialdehyde levels in the kidney. Ethanol consumption induced a significant increase in renal nitrite and nitrate levels. Treatment with ethanol increased mRNA expression of both eNOS and iNOS. Immunohistochemical assays showed increased immunostaining for eNOS and iNOS after treatment with ethanol. Kidneys from ethanol-treated rats showed increased activity of MMP-2. Histopathological investigation of kidneys from ethanol-treated animals revealed tubular necrosis. Indices of renal function and tissue injury were not altered in ethanol-treated rats. Conclusions Ethanol consumption increased renal metalloproteinase expression/activity, which was accompanied by histopathological changes in the kidney and elevated NO generation. Since iNOS-derived NO and MMPs contribute to progressive renal injury, the increased levels of NO and MMPs observed in ethanol-treated rats might contribute to progressive renal damage. (AU)

• Processo FAPESP: 06/60076-7 - Efeito do consumo crônico de etanol sobre o sistema adrenomedulina em aorta e leito mesentérico de ratos e avaliação do papel protetor desse peptídeo nas alterações vasculares induzidas pelo etanol
• Beneficiário: Carlos Renato Tirapelli
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores