Cell Biology – Immunology – Pathology
Kidney International (1999) 55, 1327–1334; doi:10.1046/j.1523-1755.1999.00358.x
Unilateral ureteral obstruction impairs renal antioxidant enzyme activation during sodium depletion
Michael Kinter, Jennifer T Wolstenholme, Barbara A Thornhill, Elizabeth A Newton, Michael L Mccormick and Robert L Chevalier
Departments of Microbiology, Pathology, and Pediatrics, University of Virginia Health Sciences Center, Charlottesville, Virginia; Research Service, VA Medical Center, and Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
Correspondence: Dr Robert L. Chevalier, Department of Pediatrics, University of Virginia, Health Science Center, Box 386, Charlottesville, Virginia 22908, USA. E-mail: rlc2m@virginia.edu
Received 24 October 1997; Revised 3 November 1998; Accepted 3 November 1998.
Abstract
Unilateral ureteral obstruction impairs renal antioxidant enzyme activation during sodium depletion.
Background
Obstructive nephropathy leads to progressive renal tubular atrophy and interstitial fibrosis and is associated with sodium wasting and sodium depletion. Renal damage resulting from unilateral ureteral obstruction (UUO) may be aggravated by reactive oxygen species (ROS), which are produced by a variety of processes. Ideally, deleterious effects of ROS are attenuated by antioxidant enzymes, including the superoxide dismutases, glutathione peroxidases, catalase, and glutathione-S-transferases. The general paradigm is that tissue damage occurs when ROS production is greater than the protective capacity of the antioxidant enzymes.
Methods
This study was designed to investigate the response of renal antioxidant 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 kidneys were harvested after 14 days, and antioxidant enzyme activities were measured 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 UUO and was doubled in sodium-depleted animals. Sodium depletion increased manganese superoxide dismutase, glutathione peroxidases, and glutathione-S-transferase activities in sham-operated kidneys but not in UUO kidneys. Relative to intact opposite kidneys, UUO kidneys had reduced activities of catalase, manganese superoxide dismutase, and glutathione-S-transferase in normal-sodium animals and all antioxidant enzymes tested in sodium-depleted animals. 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 antioxidant enzymes, consistent with a stress response to increased ROS production. Further, UUO not only reduced antioxidant enzyme activities but also inhibited increases seen with sodium depletion. We conclude that suppression of renal antioxidant enzyme activities by UUO contributes to the progression of renal injury in obstructive nephropathy, a process exacerbated by sodium depletion.
Keywords:
progressive renal failure, tubular atrophy, obstructive uropathy, reactive oxygen species, superoxide dismutase, renal injury
Abbreviations:
CuZnSOD, copper-zinc superoxide dismutase; GPx, glutathione peroxidase; GST, glutathione-S-transferase; IO, intact opposite; MnSOD, manganese superoxide dismutase; ROS, reactive oxygen species; TBARS, thiobarbituric acid reactive substances; TGF-
1, transforming growth factor-1; UUO, unilateral ureteral obstruction
