The renoprotective effects of naringin and trimetazidine on renal ischemia/reperfusion injury in rats through inhibition of apoptosis and downregulation of micoRNA-10a

Abstract

Renal Ischemia-Reperfusion (IR) injury occurs due to circulatory shock and renal transplantation, leading to mortality and morbidity worldwide. The primary purpose of the current study was to evaluate the renoprotective effects of the naringin (NAR) and trimetazidine (TMZ) on IR injury, renal hemodynamics, antioxidant capacity, microRNA-10a, and expression of apoptosis factors. Forty rats were divided into five groups randomly: Sham, IR injury, (TMZ, 5 mg/kg), (NAR pretreatment, 100 mg/kg), and TMZ plus NAR. The sham group underwent the identical surgical procedure as the other groups, except for the application of clamps. After anesthesia, IR injury was induced by 45 min of ischemia, followed by reperfusion for 4 h. Tissue and blood samples were collected for evaluation of renal function, antioxidant activity and, biochemical and molecular parameters. Administration of the NAR, TMZ, and their combination decreased the plasma level of microRNA-10a, caspase-3, and Bcl-2 associated x protein (Bax) mRNA expression, but increased the B- cell lymphoma 2 (Bcl-2) mRNA expression in the kidney tissue. In addition, antioxidant activity, renal blood flow, creatinine clearance (CCr), and fractional excretion of sodium (FENa) were improved. The NAR, TMZ, and their combination can prevent renal I/R injury through promotion of the level of antioxidant enzymes, as well as decrease of microRNA-10a and anti-apoptosis properties. Our data also suggest that NAR, TMZ, or their combination might be beneficial as potent therapeutic factors against renal IR injury.

Keywords

• Naringin
• Trimetazidine
• MicroRNA-10a
• Anti-apoptosis properties
• Renal ischemia/reperfusion injury
• Rat