Effects of allopurinol and melatonin on warm renal ischemic- reperfusion injury in dogs

It has been previously observed that reperfusion of ischemic kidneys produces much more damage than that caused by the period of ischemia alone. However, the nature of the cellular insult that produces these changes is unknown. In this study, 30 male domestic native dogs were selected and randomly divided into five groups (n=6): G1:sham-operated(sham)(n=6), G2:ischemic-reperfusion induced group(I/R); about 45 min ischemia and 3 h reperfusion (n=6) , G3: I/R+melatonin(3 mg/kg) (n=6), G4: I/R + allopurinol (10 mg/kg)(n=6), G5: I/R +allopurinol + melatonin (n=6). Unilateral ureteral obstruction by ventral midline celiotomy in the left kidney was performed and after 14 days, renal samples were taken by ultrasound guided biopsy and samples were fixed in 10% buffered formalin and sent to pathology for grading. Data were analyzed by Mann-Whitney U test. P<0.05 was considered statistically significant. The degree of protection against renal dysfunction was less in comparison to animals treated with melatonin; we would suggest that melatonin-evoked changes in glutathione content and redox state results from increased activities of the enzymes of glutathione metabolism. There are a number of possible explanations for this finding, the most likely being that factors other than oxygen free radicals (for example, irreversible loss of mitochondrial function and ATP depletion and/or activation of proteolytic enzymes) contribute to renal dysfunction as the period of ischemia is extended.