Oxygen metabolites and hypoxic renal injury: effect of mitochondrial electron transport blockade.
Isolated perfusion of the rat kidney causes hypoxic damage in the cells of the thick ascending limb of the loop of Henle. The cell damage is driven by active solute transport, which generates an imbalance of oxygen supply and demand. This injury is paradoxically prevented by adding the mitochondrial electron transport inhibitors rotenone or antimycin to the perfusion media. The present study shows that rotenone and antimycin decrease production of hydrogen peroxide in the thick ascending limb during perfusion. The findings support the hypothesis that the injury in this model is dependent on mitochondrial electron flow and suggest that mitochondrial electron flow, driven by the work of active solute transport in the presence of limited oxygen availability, may result in the generation of toxic oxygen metabolites.
Shanley
Paul F
PF
Department of Pathology, College of Medicine, State University of New York, Upstate, Syracuse 13210, USA. shanleyp@upstate.edu
Johnson
Ginger C
GC
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D010478:Chemotherapy, Cancer, Regional Perfusion; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D000860:Hypoxia / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D008138:Loop of Henle / Q000293:injuries* / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D012402:Rotenone / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014475:Uncoupling Agents; D012402:Rotenone; D002374:Catalase; D010100:Oxygen; D000640:Amitrole