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- Title
Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat.
- Authors
Chatterjee, Prabal K.; Cuzzocrea, Salvatore; Brown, Paul A.J.; Zacharowski, Kai; Stewart, Keith N.; Mota-Filipe, Helder; Thiemermann, Christoph
- Abstract
Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat. Background. The generation of reactive oxygen species (ROS) contributes to the pathogenesis of renal ischemia-reperfusion injury. The aim of this study was to investigate the effects of tempol in (1 ) an in vivo rat model of renal ischemia/reperfusion injury and on (2 ) cellular injury and death of rat renal proximal tubular (PT) cells exposed to oxidant stress in the form of hydrogen peroxide (H2 O2 ). Methods. Male Wistar rats underwent bilateral renal pedicle clamping for 45 minutes followed by reperfusion for six hours. Tempol (30 mg/kg/h), desferrioxamine (DEF; 40 mg/kg/h), or a combination of tempol (30 mg/kg/h) and DEF (40 mg/kg/h) were administered prior to and throughout reperfusion. Plasma concentrations of urea, creatinine, Na+ , γ-glutamyl transferase (γGT), aspartate aminotransferase (AST), and urinary Na+ and N-acetyl-β-d-glucosaminidase (NAG) were measured for the assessment of renal function and reperfusion injury. Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation, respectively. Renal sections were used for histologic grading of renal injury and for immunohistochemical localization of nitrotyrosine and poly(ADP-ribose) synthetase (PARS). Primary cultures of rat PT cells were incubated with H2 O2 (1 mmol/L for 4 h) either in the absence or presence of increasing concentrations of tempol (0.03 to 10 mmol/L), DEF (0.03 to 10 mmol/L), or a combination of tempol (3 mmol/L) or DEF (3 mmol/L). PT cell injury and death were determined by evaluating mitochondrial respiration and lactate dehydrogenase (LDH) release, respectively. Results. In vivo, tempol significantly reduced the increase in urea, creatinine, γGT, AST, NAG, and...
- Subjects
ISCHEMIA; CHRONIC kidney failure
- Publication
Kidney International, 2000, Vol 58, Issue 2, p658
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2000.00212.x