Partial suppressive effect of melatonin on indomethacin-induced renal injury in rat

Intramuscular injection of a single high dose of indomethacin (20 mg/kg) in fasted rats produced renal injury. The results showed increases in the level of lipid peroxidation and cholesterol, and activity of acid phosphatase and alkaline phosphatase in the kidney. Also, the renal contents of both reduced glutathione and activity of total adenosine triphosphatase were decreased by the toxicant. In serum, indomethacin increased activity of lactate dehydrogenase and acid phosphatase, and levels of creatinine and inorganic phosphorus. Paradoxically, administration of melatonin (0.75 mg/rat/day) alone for 7 days decreased significantly the activity of lipid peroxidation and acid phosphatase, and increased, but not significantly, the level of reduced glutathione in the kidney. Also, serum level of creatinine tended to decrease, but not significantly. Pretreatment with melatonin prevented the increase by subsequently administered indomethacin in the renal activity of lipid peroxidation and acid phosphatase. However, this pretreatment regimen partially suppressed the adverse changes in the remaining analyzed cytotoxic parameters induced by indomethacin in both serum and kidney. These results indicate that oral administration of melatonin at a low dose level exerted moderate antioxidant action, thereby it protected against some of the renal detrimental effects produced by indomethacin.