Abstract

NEPHROPROTECTION BY OLEANOLIC AND URSOLIC ACID AGAINST CISPLATIN IS COMPARABLE TO AMIFOSTINE

Pragnesh J. Maniya, Sarika M. Kamble, Sameer N. Goyal, Chandragouda R. Patil

ABSTRACT

OBJECTIVES: To compare the protective effects low-dose intravenously administered Oleanolic acid (OA) and Ursolic acid (UA) with intravenous amifostine (AMF) against cisplatin (CP)-induced nephrotoxicity in rats. METHODS: Nephrotoxicity was induced by intraperitoneal injection of CP (5 mg/kg). OA and UA were administered at 0.5, 1.0 and 1.5 mg/kg doses, twice a day, for 5 days post CP injection. AMF was administered intravenously at 90 mg/kg dose 30 minutes prior to CP injection. Serum and urine samples were collected for each group and the rats were sacrificed to collect kidneys for biochemical and histopathological examinations. RESULTS: In CP-treatd rats there was significant increase in the serum biomarkers of nephrotoxicity and reduction in serum alkaline phosphatase (ALPase) levels. Kidney homogenates of CP-treated rats revealed increased oxidative stress. Intravenous administration of OA and UA to CP-treated rats reduced oxidative stress by inhibiting depletion of oxidative stress markers from the kidneys. OA and UA treatments dose-dependently inhibited alternations in the serum and urine biomarkers of nephrotoxicity and oxidative stress. The kidney histology of OA and UA treated rats revealed a protection from CP-induced damage. It is noteworthy that OA and UA administered at a considerably lower dose of 0.5, 1 and 1.5 mg/ kg twice a day for five days exert protection against CPinduced nephrotoxicity comparable to intravenous AMF.CONCLUSIONS: OA and UA protected the kidney from CP-induced nephrotoxicity by inhibiting oxidative stress and have the potential to use as an adjuvants to main therapy.

Keywords: Cisplatin-induced nephrotoxicity; Oleanolic acid; Ursolic acid; Amifostine; Nephroprotection.