Unilateral ureteral obstruction impairs renal antioxidant enzyme activation during sodium depletion

Background. Obstructive nephropathy leads to progressive renal tubular atro phy and interstitial fibrosis and is associated with sodium wasting and sod ium depletion. Renal damage resulting from unilateral ureteral obstruction (UUO) may be aggravated by reactive oxygen species (ROS), which are produce d by a variety of processes. Ideally, deleterious effects of ROS are attenu ated by antioxidant enzymes, including the superoxide dismutases, glutathio ne peroxidases, catalase, and glutathione-S-transferases. The general parad igm is that tissue damage occurs when ROS production is greater than the pr otective capacity of the antioxidant enzymes. Methods. This study was designed to investigate the response of renal antio xidant enzymes to UUO and sodium depletion. Adult, male Sprague-Dawley rats received normal-sodium or sodium-depleted diets and were subjected to UUO or sham operation. Obstructed (UUO), intact opposite, or sham-operated kidn eys were harvested after 14 days, and antioxidant enzyme activities were me asured in kidney homogenates. Thiobarbituric acid reactive substances were measured in these homogenates at 3 and 14 days after UUO or sham operation as an index of ROS production. Results. Renal interstitial area, a measure of fibrosis, was increased by U UO and was doubled in sodium-depleted animals. Sodium depletion increased m anganese superoxide dismutase, glutathione peroxidases, and glutathione-S-t ransferase activities in sham-operated kidneys but not in UUO kidneys. Rela tive to intact opposite kidneys, UUO kidneys had reduced activities of cata lase, manganese superoxide dismutase, and glutathione-S-transferase in norm al-sodium animals and all antioxidant enzymes tested in sodium-depleted ani mals. Renal thiobarbituric acid reactive substances were increased by three days of UUO and were increased further by 14 days of sodium depletion. Conclusion. In summary, sodium depletion increased several renal antioxidan t enzymes, consistent with a stress response to increased ROS production. F urther, UUO not only reduced antioxidant enzyme activities but also inhibit ed increases seen with sodium depletion. We conclude that suppression of re nal antioxidant enzyme activities by UUO contributes to the progression of renal injury in obstructive nephropathy, a process exacerbated by sodium de pletion.