Cytoprotective Effect of Trimetazidine on 75 min Warm Renal Ischemia-Reperfusion Injury in Rats

Abstract

In this experimental study, we evaluated the effect of trimetazidine (TMZ) on renal ischemia-reperfusion (IR) injury in Sprague-Dawley rats. Renal IR was achieved by a 75-min clamping of the left renal pedicle and subsequent 24 h reperfusion, after right nephrectomy was performed. The rats were randomly divided into three groups: group 1 (sham operated: no IR injury), group 2 (ischemic control: saline treatment), and group 3 (3 mg/kg TMZ before ischemia). After 24 h of reperfusion, blood samples and renal tissue samples were taken to measure the levels of creatinine, tissue malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) activity. Histopathological changes were evaluated. In addition, the 7-day survival rates in each group were evaluated. We found significant increases in the levels of creatinine and tissue MDA, severe acute tubular necrosis, and a significant decrease in the activity of the GSH-Px in group 2. There were significant decreases in the levels of creatinine and tissue MDA, mild acute tubular necrosis, and a significant increase in activity of the GSH-Px in group 3 when compared with the control group (p <0.05). Statistically significant differences (p <0.05) in survival were noted between the ischemic control and sham-operated and TMZ groups. We have concluded that TMZ is able to protect the kidney from warm IR injury.

Cytoprotective effect of trimetazidine on 60 minutes of intestinal ischemia-reperfusion injury in rats

“…The decrease in the level of MDA in the TMZ group, as compared with the control group, indicated that lipid peroxidation was inhibited by this agent. Our previous study showed that TMZ significantly reduced lipid peroxidation after 75 min of warm renal ischemia followed by reperfusion injury [17]. Grekas et al have also described the inhibition of lipid peroxidation by TMZ in renal IR injury [7].…”

“…TMZ reduces intracellular accumulation of sodium and calcium and inhibits platelet ad- hesion-aggregation, neutrophil infiltration, and the generation or activity of oxygen-derived free radicals [l, 9, 221. The potent antioxidant effect of T M Z has been demonstrated in myocardial, renal, and hepatic IR injury [7,17,20,22]. A significant increase in MDA levels has been observed in various organs including the liver, kidney, and intestine during IR injury [7,16,19,23,24].…”

“…Trimetazidine (TMZ), a potent antioxidant agent, has been used to protect IR injury of the myocardium, liver, and kidney [7,17,20,22]. However, there is no report on the use of T M Z in intestinal IR injury.…”

The first histopathological evidence of trimetazidine for the prevention of contrast-induced nephropathy

“…32 The potent antioxidant effect of TMZ has been shown in renal, myocardial, and hepatic ischemia-reperfusion injury models. 33,34 The CM group in the present study had significantly lower SOD activity than the CM + TMZ group. The CM group also had a higher MDA level than the CM + TMZ group, but the difference was not significant.…”

Ischemia-Reperfusion Injury in the Transplanted Kidney Based on Purine Metabolism Markers and Activity of the Antioxidant System

“…Moreover, it has been shown that TMZ significantly reduced lipid peroxidation after 60 min warm renal ischemia followed by 15 min reperfusion (Hauet et al, 1998c). TMZ decreased also the concentrations of malondialdehyde and increased the activity of glutathione peroxidase in rat's kidney after warm ischemia (Ozden et al, 1998). Recipient treatment with trimetazidine improved graft function and protected energy status after lung transplantation (Inci et al, 2001).…”