cyclosporin-c and Acute-Kidney-Injury

Cyclosporin A (CsA) is a potent inhibitor of the Ca(2+)-dependent "pore" in isolated mitochondrial from diverse sources. Cisplatin-induced acute renal failure has been associated with morphological and functional alterations in renal cortex mitochondrial (RCM). This study was undertaken to examine the probable involvement of Ca(2+)-dependent permeabilization of RCM in cisplatin nephrotoxicity. RCM from rats injected with cisplatin (5 mg/kg body wt) 4 days earlier showed a significantly reduced capacity of retaining matrix Ca2+ and membrane potential in the presence of 15 nmol Ca2+/mg protein and 0.1 mM Pi (inorganic phosphate), compared to controls (those of rats that received carrier alone). These indices of mitochondrial dysfunction were restored to control levels when 1 microM CsA was added to assay media of RCM obtained from cisplatin-treated rats. Renal insufficiency induced by cisplatin assessed by serum creatinine and urea levels was significantly alleviated in rats 4 days after i.p. injections of cisplatin (5 mg/kg body wt) and CsA (50 micrograms/kg body wt), compared to those injected with cisplatin alone. Our findings support an involvement of Ca(2+)-mediated RCM damage in the mechanism of cisplatin nephrotoxicity, and suggest that suitable antagonists of Ca(2+)-dependent "pore" formation may improve renal tolerance to cisplatin.

Topics: Acute Kidney Injury; Animals; Antineoplastic Agents; Calcium; Cisplatin; Creatinine; Cyclosporins; Immunosuppressive Agents; Injections, Intraperitoneal; Kidney Cortex; Male; Membrane Potentials; Mitochondria; Rats; Rats, Sprague-Dawley; Urea