Protective effects of naringin and trimetazidine on remote effect of acute renal injury on oxidative stress and myocardial injury through Nrf-2 regulation.

Abstract

Ischemia/reperfusion (I/R) is the predominant cause of acute renal failure (ARF), which damages the remote organs, especially the heart, and subsequently leads to death. The aim of the current study was to examine the effects of naringin (NAR), trimetazidine (TMZ), or their combination on the Nrf-2 expression in the kidney tissue, and myocardial injury in the renal IR injury in rats. Forty male Sprague-Dawley rats were randomly separated into five groups as follows: sham, IR injury, TMZ (5 mg/kg, intravenously), NAR (100 mg/kg), and their combination. Renal I/R injury and ischemia were induced by using clamps for 45 min, and after 4 h reperfusion, respectively. Then, the Nrf-2 expression in the kidney, antioxidant activity (CAT, SOD, and GPx), total antioxidant capacity (TAC), oxidative stress, electrocardiogram (ECG) parameters, and biochemical markers were examined. Renal IR injury significantly reduced the Nrf-2 expression, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) enzymes' activities and TAC. Moreover, Malondialdehyde (MDA) level in kidney and heart tissues, plasma creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH) activity were increased, and ECG parameters were significantly distributed; however, NAR, TMZ, or their combination improved these changes, in comparison with the renal IR injury in rats. NAR, TMZ, or their combination could attenuate the Nrf-2 expression in the kidney tissue, following the renal IR injury through inhibition of lipid peroxidase, and enhancement of antioxidant activity.