Protective Effects of the Angiotensin II Receptor Blocker Losartan on Cisplatin-Induced Kidney Injury

Abstract

Background: In the present study, we investigated the possible modulatory effect of losartan, an angiotensin receptor blocker, on oxidative stress induced by cisplatin (CDDP) as well as on CDDP uptake by the kidney. Methods: Rats were injected with a single dose of CDDP (7 mg/kg) and/or losartan (in either a single dose of 60 mg/kg or divided doses (10 mg/kg daily for 6 days), starting 1 h before CDDP injection. In addition, rat renal cortical slices were incubated with CDDP (2 mM) and/or losartan (2 mM) for 4 h. Nephrotoxicity was evaluated by measuring serum creatinine and blood urea nitrogen (BUN) in vivo and lactate dehydrogenase (LDH) leakage in vitro; histopathological examination of kidney tissue was also done. Oxidative stress markers including reduced glutathione (GSH) and lipid peroxides were also assessed. Furthermore, CDDP uptake by renal cortical slices was determined. Results: Losartan has protective effects against CDDP-induced nephrotoxicity as evidenced by restoration of normal serum levels of creatinine and BUN, and LDH leakage. Histopathological examination of the kidney confirmed these results. Also, losartan significantly counteracted CDDP-induced lipid peroxidation and GSH depletion. However, losartan did not affect CDDP uptake by the kidney. Conclusion: Our results indicate that losartan has proved to be a promising drug for clinical use as a nephroprotectant against CDDP-induced nephrotoxicity.