RESUMEN
The present study was designed to examine whether lithospermic acid B (LSB) isolated from Salvia miltiorrhiza has an ameliorative effect on renal functional parameters in association with the expression of aquaporin 2 (AQP 2) and Na,K-ATPase in the ischemia-reperfusion induced acute renal failure (ARF) rats. LSB showed strong antioxidant activity against production of reactive oxygen species (ROS), ROS-induced hemolysis, and production of lipid peroxide in a dose-dependent manner. Polyuria caused by down-regulation of renal AQP 2 in the ischemia-reperfusion induced ARF rats was partially restored by administration of LSB (40 mg/kg, i.p.), restoring expression of AQP 2, in renal inner and outer medulla. The expression of Na,K-ATPase alpha1 subunit in outer medulla of the ARF rats was also restored in the ARF rats by administration of LSB, while beta1 subunit level was not altered. The renal functional parameters including creatinine clearance, urinary sodium excretion, urinary osmolality, and solute-free reabsorption were also partially restored in ischemia-ARF rats by administration of LSB. Histological study also showed that renal damages in the ARF rats were abrogated by administration of LSB. Taken together, these data indicate that LSB ameliorates renal defects in rats with ischemia-reperfusion induced ARF, most likely via scavenging of ROS.
Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Benzofuranos/farmacología , Inhibidores Enzimáticos/farmacología , Daño por Reperfusión/tratamiento farmacológico , Salvia miltiorrhiza/química , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Animales , Acuaporina 2 , Acuaporinas/antagonistas & inhibidores , Acuaporinas/biosíntesis , Benzofuranos/aislamiento & purificación , Western Blotting , Depsidos , Inhibidores Enzimáticos/aislamiento & purificación , Eritrocitos/efectos de los fármacos , Depuradores de Radicales Libres/farmacología , Hemólisis/efectos de los fármacos , Radical Hidroxilo/metabolismo , Técnicas In Vitro , Riñón/metabolismo , Riñón/patología , Pruebas de Función Renal , Peroxidación de Lípido/efectos de los fármacos , Masculino , Oxidantes/metabolismo , Raíces de Plantas/química , Proteínas/metabolismo , Ratas , Ratas Sprague-Dawley , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , ATPasa Intercambiadora de Sodio-Potasio/biosíntesis , Superóxidos/metabolismoRESUMEN
A pharmacological inhibition of nitric oxide synthase (NOS) in rats for 4-6 weeks produces renal vasoconstriction, renal dysfunction, and severe hypertension. The present study was aimed at investigating whether Cudrania tricuspidata (C. tricuspidata) water extract ameliorates N(G)-Nitro-L-arginine methylester (L-NAME)-induced hypertension. Treatment of L-NAME (60 mg/L drinking water, 4 weeks) causes a sustained increase in systolic blood pressure (SBP). The concentration of plasma NO metabolites and NO/cGMP productions in the vascular tissues of the L-NAME-treated group were significantly reduced as compared with those in the control. C. tricuspidata water extract blocked increase of SBP in the L-NAME-treated group and restored SBP to normal level. Futhermore, C. tricuspidata water extract was able to preserve the vascular NO/cGMP production and plasma NO metabolites concentration. However, there are no changes in the expression of ecNOS and iNOS of thoracic aorta among the rats of control, L-NAME-treated group, and L-NAME and C. tricuspidata water extract co-treated group. The urinary sodium level, urine volume, and creatinine clearance were significantly higher in rats co-treated with C. tricuspidata water extract and L-NAME than in L-NAME-treated group. Taken together, these results suggest that C tricuspidata water extract prevents the increase of SBP in the L-NAME-induced hypertension that may have been caused by enhanced generation of vascular NO/cGMP.