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Chaetomellic acid A treatment improves oxidative stress in rats with renal mass reduction

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Resumo:Chaetomellic acid A (CA) is a potent and highly specific inhibitor of Ras farnesyl-protein transferase that has shown to decrease oxidative stress in rats with brain damage. Oxidative stress has been suggested to play an important role in the pathogenesis of chronic renal disease. Thus, the aim of this work was to evaluate the effect of chronic treatment with CA on oxidative stress in a model of renal mass reduction. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been placed in four experimental groups: RMR rats without treatment (n=12); RMR rats treated with CA (n=8); SO rats without treatment (n=13); SO rats treated with CA (n=13). CA was intraperitoneally administered in a dose of 0.23 μg/Kg three times a week for six months. To evaluate the effect of CA on renal redox potential, the status of oxidative stress in renal tissues was determined. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity, and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CA administration significantly increased catalase and GR activity (p<0.05), and increased GSH/GSSG ratio, but no significant difference between the treated and no treated groups was found in this ratio. These data suggest that CA can attenuate 5/6 RMR-induced oxidative stress and therefore, contribute to prevention of progressive renal failure in chronic renal disease.
Autores principais:Nogueira, António José M.
Outros Autores:Oliveira, Paula A.; Colaço, Bruno Jorge; Oliveira, Maria; Peixoto, Francisco P.; Pires, Maria João
Assunto:Chaetomellic acid a Oxidative stress
Ano:2013
País:Portugal
Tipo de documento:documento de conferência
Tipo de acesso:acesso aberto
Instituição associada:Instituto Politécnico de Bragança
Idioma:inglês
Origem:Biblioteca Digital do IPB
Descrição
Resumo:Chaetomellic acid A (CA) is a potent and highly specific inhibitor of Ras farnesyl-protein transferase that has shown to decrease oxidative stress in rats with brain damage. Oxidative stress has been suggested to play an important role in the pathogenesis of chronic renal disease. Thus, the aim of this work was to evaluate the effect of chronic treatment with CA on oxidative stress in a model of renal mass reduction. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been placed in four experimental groups: RMR rats without treatment (n=12); RMR rats treated with CA (n=8); SO rats without treatment (n=13); SO rats treated with CA (n=13). CA was intraperitoneally administered in a dose of 0.23 μg/Kg three times a week for six months. To evaluate the effect of CA on renal redox potential, the status of oxidative stress in renal tissues was determined. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity, and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CA administration significantly increased catalase and GR activity (p<0.05), and increased GSH/GSSG ratio, but no significant difference between the treated and no treated groups was found in this ratio. These data suggest that CA can attenuate 5/6 RMR-induced oxidative stress and therefore, contribute to prevention of progressive renal failure in chronic renal disease.