Protective effect of Phyllanthus niruri against cyclosporine A-induced nephrotoxicity in rats

Abstract

Phyllanthus niruri (Euphorbiaceae) is a popular plant in folk medicine, whole plant, fresh leaves, and fruits are used in the treatment of various diseases. In the present study, nephroprotective potential of aqueous extract of P. niruri was investigated against cyclosporine A (CsA) induced changes in kidney of Wistar rats. Nephrotoxicity was induced by oral administration of CsA (25 mg/kg/b.w.) dissolved in olive oil for a period of 21 days. Nephrotoxicity induced rats were treated with aqueous extract of P. niruri (200 mg/kg/b.w.) for a period of 21 days. Levels of serum creatinine and blood urea nitrogen, renal marker enzymes in serum and different enzymic and non-enzymic antioxidants, lipid peroxidation products, as well as ATPases in kidney homogenates were measured in normal, control (toxicity induced), and P. niruri treated rats. Histopathological studies were also been carried out. Administration of CsA increased the serum levels of creatinine and blood urea nitrogen, alkaline phosphatase, alanine aminotransaminase, and lactate dehydrogenase thereby indicating damage to kidneys. Increased lipid peroxidation and a decrease in antioxidants enzymes were observed in toxicity-induced rats. The levels of membrane-bound ATPases were also significantly altered. Upon administration of P. niruri, the levels of serum creatinine and blood urea nitrogen and also lipid peroxidation were found to be markedly reduced. Renal antioxidant defense systems, such as superoxide dismutase, catalase, glutathione peroxidase activities and reduced glutathione, and vitamins e and c, depleted by cyclosporine A, were restored to normalcy by treatment with the extract. The drug also effectively attenuated renal dysfunction and normalized the altered renal morphology and also restored the activities of renal ATPases. The results suggest that the nephroprotective effect of P. niruri could be due to the inherent antioxidant and free-radical scavenging principle(s) contained in the extract. In conclusion, our study indicates that P. niruri through its antioxidant activity effectively salvaged CsA induced nephrotoxicity.