Effect of cisplatin on renal brush border membrane enzymes and phosphate transport

Abstract

Cisplatin (CDDP) is widely used in the treatment of various cancers but its clinical use is associated with dose limiting nephrotoxicity. The present work was carried out to study the effect of administration of CDDP on rat renal brush border membrane (BBM) marker enzymes and inorganic phosphate (Pi) transport across BBM vesicles (BBMV). Animals were administered a single intraperitoneal dose of CDDP (6 mg/kg body weight) or normal saline and then sacrificed 2, 4, 8 and 16 days after this treatment. The administration of CDDP resulted in increased serum creatinine and blood urea nitrogen levels and decreased activity of BBM marker enzymes in the BBM as well as in the homogenates of cortex and medulla. Kinetic studies showed that the Vmax of the enzymes was decreased in BBM from CDDP treated rats while the Km remained unchanged. The Na+ -gradient dependent transport of Pi across BBMV was also significantly reduced after CDDP treatment. These results strongly suggest that the administration of a single nephrotoxic dose of CDDP results in impairment of the functions of renal BBM.