Amelioration Of Rat Renal Ischemia-Reperfusion Injury By MnTBAP (A SOD-Mimetic) In An In Vivo Model

Document Type : Original Article




Introduction: Ischemia-reperfusion (IR) injury involves a complex, interrelated sequence of events. Generation of reactive oxygen species (ROS) especially superoxide anion, during IR is reported. The present study was designed to investigate the effect of Mn (III) tetrakis (4- benzoic acid) porphyrin (MnTBAP), an active, stable, nontoxic, and cell permeable SOD (super oxide dismutase) mimetic in prevention of renal IR injury. It is very important that MnTBAP, possesses both SOD and catalase activity.
Material and Methods: Experiments were performed on pentobarbital anesthetized rats. After tracheotomy, the femoral artery was cannulated and mean arterial pressure and heart rate were recorded for the duration of the experiment using a PowerLab/4sp data acquisition system. All groups received a continuous saline infusion with a rate of 6 ml/kg/h (through the femoral vein). Bladder was cannulated and urine was collected throughout the reperfusion (6h) periods. A midline laparatomy was performed and the renal arteries were carefully separated from around tissues. After surgery and stabilization period (60 min), animals were randomly assigned to the four groups: Sham operated Sham+ MnTBAP, IR, IR + MnTBAP. In the IR groups, rats were subjected to bilateral renal artery occlusion for 40 min followed by 6 h reperfusion. Rats were administered either MnTBAP (10 mg/kg IV bolus 15 min prior to IR) or saline. Data were analyzed by one way ANOVA.
Results: Renal IR resulted in significant increases in creatinine, BUN, aspartate aminotransferase (AST), Fractional excretion of Na+ (FENA+) and urinary N-acetyl-?-D-glucosaminidase (NAG) activity and MnTBAP significantly reduced the IR mediated increases in creatinine, BUN, FENa+, AST and NAG.
Conclusion: These results suggest that MnTBAP reduce the renal dysfunction and injury associated with IR. Thus, a SOD-mimetic like MnTBAP, should be considered in the treatment of renal I/R injury.