Evidence against oxidant injury as a critical mediator of postischemic acute renal failure.
The purpose of this study is to confirm previous evidence for reactive oxygen species (ROS) as critical mediators of postischemic renal injury by documenting lipid peroxidation after ischemic-hypoxic insults and by demonstrating that antioxidants confer protection. Renal malondialdehyde (MDA) concentrations, an index of lipid peroxidation, were measured using uncorrected and tissue-chromagen-corrected methods in 1) cortical (C), outer medullary stripe (OMS), inner medullary (IM) whole renal tissues, and C and OMS mitochondria obtained 15 min after in vivo renal artery occlusion (RAO; x 45 min); 2) C, OMS, and IM whole tissues obtained 15 min after completing 45 min of ischemia in an isolated perfused kidney; and 3) isolated proximal tubular cell (PTC) suspensions after 45 min of hypoxia with 15 min of reoxygenation. Despite significant oxygen deprivation-induced injury in each of these systems, no significant rise in MDA concentrations could be documented, with the sole exception of the in vivo IM region (by uncorrected MDA assay only). The latter rise could be attributed to medullary vascular congestion causing a hemoglobin-induced artifact in the MDA assay. Sixty-minute in vivo RAO plus reflow also did not raise MDA. To validate the MDA assay 4.2 mM H2O2 was added to PTC. An abrupt fourfold rise in MDA resulted. Pretreatment of 30- and 45-min RAO rats with two antioxidants (allopurinol or superoxide dismutase) failed to confer functional or morphological protection. We conclude that ROS may not be critical consistent mediators of in vivo postischemic acute renal failure.
Department of Medicine, University of Washington, Seattle.
L M
LM
Gamelin
R A
RA
Zager
D058186:Acute Kidney Injury / Q000503:physiopathology*; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008054:Lipid Peroxides / Q000502:physiology*; D008314:Malonates / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology
D008054:Lipid Peroxides; D008314:Malonates; D008315:Malondialdehyde; D000493:Allopurinol; D013482:Superoxide Dismutase