ROLE OF INTRINSIC ANTIOXIDANT ENZYMES IN RENAL OXIDANT INJURY

To investigate the functional role of renal intrinsic antioxidant enzymes (AOEs), the levels of AOE activities in isolated glomeruli and the changes in renal function to oxidant insults were assessed in normal control rats (NC, N = 23) and rats subjected to 30-minutes of complete renal ischemia for three days (day-3, N = 20) or six days (day-6, N = 23) prior to study. When compared to NC, the activities of total and manganese (cyanide-insensitive) superoxide dismutase, glutathione peroxidase, and catalase were increased more than twofold in day-6 animals, on average, from 36 ± 4 U/mg protein, 9 ± 1 U/mg protein, 129 ± 21 U/mg protein and 1.32 ± 0.20 k/mg protein, respectively, to 80 ± 5, 27 ± 3, 283 ± 41 and 3.20 ± 0.20, respectively (P < 0.05 for all). There were no changes in AOE activities in day-3 animals. In day-6 animals, however, the activities of non-AOEs, LDH and fumarase were found to be unaffected. Separate groups of NC (N = 12), day-3 (N = 5) and day-6 (N = 12) rats were subjected to either 30 minutes of ischemia plus 60 minutes of reperfusion (I/R) or unilateral i.a. infusion of hydrogen peroxide (H2O2, 35 μmoles in 1 hr). The degree of reduction in inulin and para-amino hippurate clearance rates following I/R were significantly less in day-6 (-21 ± 3% and -12 ± 2, respectively) compared to NC (-69 ± 9% and -59 ± 11, respectively) or day-3 rats (-73 ± 7% and -62 ± 10, respectively). Likewise, whereas urine protein excretion rate increased markedly following H2O2 administration in NC (from 4 ± 1 μg/min to 309 ± 29), proteinuria did not develop in day-6 (from 5 ± 1 g/min to 5 ± 3). These findings suggest that renal intrinsic AOE activities can be augmented by the insult of I/R, and the enhanced AOE activities provide kidneys with an effective defense system against ROS-mediated injuries. Thus, the prevailing AOE activity levels within the kidney appear to be an important determinant for renal dysfunction induced by ROS.