Hemin attenuates cisplatin-induced acute renal injury in male rats.

Mohamed A Al-Kahtani,Omar M Elmenshawy,Mohamed A El-Kersh,Ashraf M Abdel-Moneim

doi:10.1155/2014/476430

Abstract

Background. The aim of this study is to investigate the protective effects of hemin (the heme oxygenase-1 [OH-1] inducer) against nephrotoxic effects induced by cisplatin [cis-diamminedichloroplatinum II (CP)] in male rats. Methods. The evaluation was performed through monitoring renal redox parameters: lipid peroxidation (LPO), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione reductase (GR), and reduced glutathione (GSH). The work also examined renal function tests (urea and creatinine), tissue proinflammatory mediator like nitric oxide (NO), and kidney cytopathology. Results. A single intraperitoneal dose of CP (10 mg/kg b.w.) caused significant elevation of blood urea, serum creatinine, and renal LPO and NO, along with significant decline of the activities of GPx and GR, but renal SOD activity and GSH level were statistically insignificant as compared to control group. Subcutaneous injection of hemin (40 µmol/kg b.w.) partially ameliorated CP-induced renal damage, based on suppression of blood urea, serum creatinine, the renal MDA and NO levels, and increased antioxidant capacity in CP-treated rats. The results of histopathological and ultrastructural investigations supported the renoprotective effect of hemin against CP-induced acute toxicity. Conclusion. The induction of HO-1 by hemin is a promising approach in the treatment of CP-induced nephrotoxicity. However, further preclinical studies are warranted to test effectiveness of CP/hemin on the outcome of tumor chemotherapy.

Highlights

Cisplatin (cis-diamminedichloroplatinum(II), cis-diamminedichloroplatinum II (CP)) is a highly effective chemotherapeutic agent against a large spectrum of tumor types [1,2,3]
With respect to Thiobarbituric Acid Reactive Substances (TBARS), renal levels were significantly higher in CP group than the control values, while TBARS levels were similar in CP plus hemin and control groups
In rats treated with hemin plus CP, the activity of NO synthetase (NOS) was decreased by 36.2% compared to CP-treated animals

Summary

Introduction

Cisplatin (cis-diamminedichloroplatinum(II), CP) is a highly effective chemotherapeutic agent against a large spectrum of tumor types [1,2,3]. Previous studies have shown that HO-1-inducing agents, as hemin, can mitigate nephrotoxic effects caused by a wide array of stressors, including mercury [15] and acetaminophen [20]. Based on the previous information, the present study aimed to examine whether the activation of HO-1 (by hemin) would have protective effects against CP. The aim of this study is to investigate the protective effects of hemin (the heme oxygenase-1 [OH-1] inducer) against nephrotoxic effects induced by cisplatin [cis-diamminedichloroplatinum II (CP)] in male rats. The work examined renal function tests (urea and creatinine), tissue proinflammatory mediator like nitric oxide (NO), and kidney cytopathology. Subcutaneous injection of hemin (40 μmol/kg b.w.) partially ameliorated CP-induced renal damage, based on suppression of blood urea, serum creatinine, the renal MDA and NO levels, and increased antioxidant capacity in CP-treated rats. Further preclinical studies are warranted to test effectiveness of CP/hemin on the outcome of tumor chemotherapy

Objectives

Methods

Results

Conclusion