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PLoS One ; 9(6): e97452, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24940871

RESUMO

Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v.) and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L). By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3')-O-(4-benzoylbenzoyl) adenosine5'-triphosphate (specific agonist) and adenosine triphosphate (nonspecific agonist) (all p<0.05). All these alterations were reduced in diabetic rats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy) in DM groups. Lipoperoxidation was strongly correlated with P2X(7) receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7) receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy.


Assuntos
Acetilcisteína/farmacologia , Albuminúria/prevenção & controle , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/terapia , Nefropatias Diabéticas/prevenção & controle , Receptores Purinérgicos P2X7/genética , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Administração Oral , Albuminúria/metabolismo , Albuminúria/fisiopatologia , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/fisiopatologia , Terapia por Exercício , Expressão Gênica , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo , Condicionamento Físico Animal , Agonistas do Receptor Purinérgico P2X/farmacologia , Ratos , Ratos Wistar , Receptores Purinérgicos P2X7/metabolismo , Estreptozocina
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