title: Post-hypoxic cellular disintegration in glycine-preserved renal tubules is attenuated by hydroxyl radical scavengers and iron chelators.
abstract: BACKGROUND
  Cellular stress during reoxygenation is a common phenomenon in solid organ transplantation and is characterized by production of reactive oxygen species. Herein, we studied in isolated tubular segments of rat kidney cortex the impact of oxygen radical scavengers and an iron chelator on post-hypoxic recovery.
  
  
  METHODS
  Tubules, suspended in Ringer's solution containing 5 mM glycine, underwent 30 min hypoxia and 60 min reoxygenation. Untreated tubules served as controls. Hypoxia-reoxygenation injury was measured by membrane leakage, lipid peroxidation and cellular functions. In hypoxia-reoxygenated-isolated tubular segments, protective effects of different scavengers and of the iron chelator deferoxamine on hypoxia-reoxygenation injury were analyzed.
  
  
  RESULTS
  Scavengers protected isolated tubular segments from hypoxia-reoxygenation-induced cellular disintegration and dysfunction. Deferoxamine was found to exert the most distinct protection. It was further found to exert a dose-dependent protection on hypoxia-reoxygenation damage in isolated tubular segments, which was critically mediated by chelating tissue and bond iron.
  
  
  CONCLUSIONS
  Our data demonstrate that radical scavengers effectively protect from hypoxia-reoxygenation injury in isolated tubular segments and that the iron chelator deferoxamine is especially a potent inhibitor of iron ion-mediated hypoxia-reoxygenation damage. Thus, inclusion of this iron chelator in organ storage solutions might improve post-transplant organ function and protect from reperfusion injury.
authors.affiliation: Department of General, Visceral, Vascular and Pediatric Surgery, University of Saarland, Homburg, Saarland, Germany.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Moussavian
authors.forename: Jan E
authors.initials: JE
authors.lastname: Slotta
authors.forename: Otto
authors.initials: O
authors.lastname: Kollmar
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Gernot
authors.initials: G
authors.lastname: Gronow
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schilling
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects*; D003593:Cytoplasm / Q000201:enzymology; D004798:Enzymes / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007511:Ischemia / Q000473:pathology*; D007684:Kidney Tubules / Q000098:blood supply* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D004798:Enzymes; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D019188:Organ Preservation Solutions; D017392:Thiobarbituric Acid Reactive Substances; D017665:Hydroxyl Radical; D007770:L-Lactate Dehydrogenase; D005969:Glutamate Dehydrogenase; D011188:Potassium; D005998:Glycine