Effect of trimetazidine on xanthine oxidoreductase expression in rat kidney with ischemia--reperfusion injury.

ABSTRACT

Ischemia/reperfusion (I/R) injury is often responsible for delayed graft function after transplantation. Trimetazidine (TMZ) is an anti-ischemic and antioxidant agent used to protect grafts from I/R injury. With the supply of molecular oxygen upon reperfusion of ischemic tissues, xanthine oxidoreductase (XOR) metabolizes xanthine and hypoxanthine to uric acid and free radicals are generated. The aim of the study was to examine the effect of TMZ on XOR expression in rat kidney with I/R injury. The study was carried out on Wistar rats divided into two groups animals treated with TMZ and control group receiving placebo. TMZ (10 mg/kg/day) was administered for 30 days. There were no significant differences in XOR expression in kidneys without ischemia between rats treated with TMZ and control group, whereas the XOR expression in kidneys with ischemia was significantly decreased in rats treated with TMZ as compared with control animals. The XOR expression in ischemic kidney was significantly lower in comparison with kidney without ischemia in the group treated with TMZ. We suggest that the decrease in xanthine oxidoreductase expression is one of the beneficial mechanisms of TMZ on I/R injury, preventing the degradation of purine nucleotides during the oxidation of hypoxanthine to xanthine and uric acid and formation of free radicals.