Study The Effect of Levosimendan in Cisplatin-Induced Nephrotoxicity in Experimental Rats

Abstract

Background: Cisplatinis  used in the treatment of many types of cancer but its used is limited mainly due to its nephrotoxicity.Levosimendan is used in  the treatment of chronic heart failure. addition  it had anti-inflammatory antioxidative,and anti-apoptotic effects.

Aim: Theaim of the present study was to investigate  thepotential beneficial effects of levosimendan in cisplatin-induced nephrotoxicity.

Materials and Methods:36 Sprague Dawley Rats were allocated  into six groups (n = 6). The first, second and third groups received normal saline (control) ;intraperitoneal (i.p.) cisplatin (6 mg/kg) on day 7, and levosimendan (2 mg/kg/day, orally for 10 consecutive days) respectively. The Fourth; Fifth  and sixth groups received a single intraperitoneal (i.p.) injection of Cis on day 7 and levosimendan (1 , 2,3 mg/kg/day, orally) for 10 days, respectively. At day 11, animals we measured   renal blood flow. biochemical, histopathological and hemodynamic studied were done.

Results:Levosimendanin dose dependantmanner  reducedCis-induced increase in plasma urea, creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels and decrease in creatinine clearance. Levosimendan reducedCis-induced increase in urinary albumin/creatinine ratio, N-Acetyl-β-D-Glucosaminidase (NAG) and kidney Injury Molecule-1 (KIM-1). Levosimendan significantly attenuated the effect of Cis on plasma concentration of plasma tumor necrosis factor–alpha (TNF-α), antioxidant indices catalase and superoxide dismutase (SOD) and lipid peroxidation. Levosimendan attenuated the remarkable renal damage and reduced renal blood flow induced by Cis.

conclusion this study shows that levosimendanin dose dependat manner has a protective effect on Cis-induced nephrotoxicity. The protective effect of levosimendan is shown to be related to its anti-inflammatory, antioxidant and vasodilator effects.