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Archivos Venezolanos de Farmacología y Terapéutica
versión impresa ISSN 0798-0264
Resumen
CAMACHO, Elsa y ISRAEL, Anita. Effect of apocynin on renal alterations induced during experimental preeclampsia in the rat. AVFT [online]. 2014, vol.33, n.4, pp.80-88. ISSN 0798-0264.
Preeclampsia (PE) is a multisystem disorder of pregnancy characterized by hypertension, proteinuria and edema. PE is associated with endothelial dysfunction, oxidative stress and decreased endothelial nitric oxide synthase activity. The mechanisms of normal pregnancy-associated vasodilatation suggest that nitric oxide (NO) is the most important mediator for the reduction of vascular resistance. Many studies demonstrated reduction of endothelium-dependent dilator response mediated by NO in PE. It has been shown that the inhibition of NO synthesis by chronic administration of L-NAME to pregnant rats results in an animal model which causes a PElike syndrome, which is associated with hypertension, renal failure, proteinuria, increased superoxide anion production and a reduction of the kidney activity of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX). Due to the important role of oxidative stress in the PE, in this study we evaluated whether inhibition of the production of reactive oxygen species uncoupling NAD(P)H oxidase with apocynin, could prevent signs of experimental PE in rats. For this purpose, we determined the effect of apocynin on the number and the weight of the fetuses, mean blood pressure, proteinuria, urinary excretion of sodium and potassium and the activity of the renal cortex enzymes CAT, SOD and GPx, in an experimental model of preeclampsia induced by treatment with L-NAME in rats of 13 days of gestation. Chronic treatment with L-NAME in pregnant rats increased MAP (+20 mmHg), produced proteinuria and reduced the weight of the fetuses. The inhibition of nitric oxide synthesis in pregnant rats reduced the activity of the three antioxidants enzymes evaluated. Chronic treatment with apocynin, prevented the increase in blood pressure, proteinuria, volume reduction and decreased urinary excretion of sodium and potassium as well as the reduction of antioxidant enzyme activity induced by L-NAME in pregnant rats. These findings suggest that impaired renal function observed in the experimental PE is associated with the reduction of antioxidant activity which is prevented by apocynin treatment. Also indicate that these actions are mediated by increased production of reactive oxygen species, in consequence the therapeutic use of antioxidants as pharmacological strategy to prevent preeclampsia seems promising.
Palabras clave : preeclampsia; apocynin; catalase; superoxide dismutase; gluthation peroxidase.