Renoprotective Effects of Edaravone in a Model of Acute kidney Injury Induced by Rhabdomyolysis in Rats, the Involvement of Nitric oxide

Abstract

Edaravone is a free radical scavenger which is used as a drug for the treatment of cerebral infarction and amyotrophic lateral sclerosis. Edaravone is distributed widely in the body and its effects are not limited to the neural tissue. Many studies indicate that edaravone has some nitric oxide synthase (NOS) modulating properties. In this research we evaluated the effects of edaravone (1, 5 and 10 mg/kg) alone or in concombination with diphenyliodonium chloride (a specific endothelial NOS inhibitor) or aminoguanidine (a specific inducible NOS inhibitor) on oxidative stress, and renal tissue and function in a model of acute kidney injury induced by a single intramuscular injection of hypertonic glycerol solution. Effects of edaravone on gene expressions of eNOS and iNOS (by RT-PCR) were also investigated. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey’s test. At the end of this study, edaravone attenuated oxidative stress and improved renal tissue damage and dysfunction. Aminoguanidine enhanced the renoprotective effects of edaravone. Edaravone showed no remarkable effect on the expression of eNOS gene but it reduced the induction of iNOS gene significantly. The results of this study showed that edaravone could protect against rhabdomyolysis-induced acute kidney injury using its antioxidant activity and inhibiting effect on iNOS gene expression.

Keywords

• edaravone
• oxidative stress
• rhabdomyolysis
• acute kidney injury
• nitric oxide