Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in anin vivorat model of renal ischemia-reperfusion

Abstract

Renal ischemia reperfusion (I/R) injury, which occurs during renal surgery or transplantation, is the major cause of acute renal failure. Trimetazidine (TMZ), an anti-ischemic drug, protects kidney against the deleterious effects of I/R. However its protective mechanism remains unclear. The aim of this study is to examine the relevance of Akt, endothelial nitric oxide synthase (eNOS), and hypoxia inducible factor-1a (HIF-1a) on TMZ induced protection of kidneys against I/R injury. Wistar rats were subjected to 60 min of warm renal ischemia followed by 120 min of reperfusion, or to intraperitoneal injection of TMZ (3 mg/kg) 30 min before ischemia. In sham operated group renal pedicles were only dissected. Compared to I/R, TMZ treatment decreased lactate dehydrogenase (845 ± 13 vs. 1028 ± 30 U/L). In addition, creatinine clearance and sodium reabsorption rates reached 105 ± 12 versus 31 ± 11 mL/min/g kidney weight and 95 ± 1 versus 68 ± 5%, respectively. Besides, we noted a decrease in malondialdehyde concentration (0.33 ± 0.01 vs. 0.59 ± 0.03 nmol/mg of protein) and an increase in glutathione concentration (2.6 ± 0.2 vs. 0.93 ± 0.16 mg GSH/mg of protein), glutathione peroxidase (95 ± 4 vs. 61 ± 3 mg GSH/min/mg of protein), and superoxide dismutase (25 ± 3 vs. 11 ± 2 U/mg of protein) and catalase (91 ± 12 vs. 38 ± 9 mmol/min/mg of protein) activities. Parallely, we noted a significant increase in p-Akt, eNOS, nitrite and nitrate (18 ± 2 vs. 8 ± 0.1 pomL/mg of protein), HIF-1a (333 ± 48 vs. 177 ± 14 mg/mg of protein) and heme oxygenase-1 (HO-1) levels regarding I/R. TMZ treatment improves renal tolerance to warm I/R. Such protection implicates an activation of Akt/eNOS signaling pathway, HIF-1a stabilization and HO-1 activation.

Protective Effects of Shenfu Injection against Myocardial Ischemia–Reperfusion Injury <i>via</i> Activation of eNOS in Rats

“…In the present experiment, we demonstrated that SFI increased eNOS phosphorylation and NO production by enhancing Akt phosphorylation, which is agreement with the report from Wang et al, who showed that ginsenoside Rg3, a main component of SFI, mediated a cardioprotective effect against MIRI-induced apoptosis via Akt/eNOS signaling. 41) Trimetazidine is a piperazine-derived agent with protective effects that is effective in the treatment of myocardial, renal and liver ischemia/reperfusion injury in which the Akt/eNOS signaling pathway is involved. 42) The results of the present study are similar to those reported in an in vivo rat model of IR.…”

Cigarette Smoke Extract Changes Expression of Endothelial Nitric Oxide Synthase (eNOS) and p16(INK4a) and is Related to Endothelial Progenitor Cell Dysfunction

“…A deficiency of eNOS-derived NO exacerbates the early stage of non-alcoholic steatohepatitis pathogenesis in a mouse model via the regulation of hepatic tissue blood flow [27]. eNOS is important in the progress of neovasculogenesis [28] and participates in various disorders by various signaling pathways [29–31]. eNOS plays a central role in the maintenance of endothelial homeostasis [32].…”

Myocardial Cytoprotector Trimetazidine Mb-Preparat, Increases the Effectiveness of Treatment of Chronic Heart Failure and Coronary Heart Disease

“…Ряд экспериментальных и клинических исследований позволяют предполагать наличие у триметазидина нефро-протективного эффекта [78][79][80][81][82]. Например, при назначе-нии триметазидина МВ за 2 дня до проведения инвазив-ных коронарных процедур (коронарография и др.)…”