Reduced activity of antioxidant enzymes underlies contrast media-induced renal injury in volume depletion.
Oxidant-mediated renal injury has been suggested as an important mechanism of acute renal failure induced by contrast media. Since volume depletion has been recognized as a predisposing factor for contrast media nephropathy, the present study was designed to characterize host-defense mechanisms against oxidant-mediated renal injury during volume depletion. Antioxidant enzyme activities in renal cortex were compared between acutely water deprived (WD, 72 hours) and non-WD rats. WD rats had reduced activities of catalase and superoxide dismutase activities (on average, 48% and 60% of values in non-WD, respectively). In separate groups of WD rats, saline or one of three different contrast media, namely diatrizoate meglumine/diatrizoate sodium (DTZ), ioxaglate meglumine/ioxaglate sodium (IXG), and iohexol (IHX) was injected. Both GFR and renal plasma flow rate, measured 24 hours later, was some 50% less in DTZ-injected than saline-injected WD rats. WD rats treated with IXG and IHX had similar GFR to saline-treated rats. In DTZ-treated WD rats, specific products of membrane lipid peroxidation, phosphatidylcholine and phosphatidylethanolamine hydroperoxide, determined by chemiluminescent HPLC, were more than two-fold higher than saline, IXG, or IHX-treated WD rats. DTZ did not induce renal dysfunction and enhance lipid peroxidation in non-WD rats. Therefore, DTZ appeared to induce oxidant-mediated injury only in WD rats. When WD rats were pretreated with polyethylene glycol-coupled catalase (1.4 mg x 2 days), renal cortical catalase activity remained at a level similar to that of non-WD rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Yoshioka
T
T
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Fogo
A
A
Beckman
J K
JK
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001834:Body Water / Q000378:metabolism; D002374:Catalase / Q000494:pharmacology; D003287:Contrast Media / Q000009:adverse effects*; D003973:Diatrizoate / Q000494:pharmacology; D004326:Drinking; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007672:Kidney Cortex / Q000201:enzymology; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology; D014868:Water Deprivation / Q000502:physiology*
D000975:Antioxidants; D003287:Contrast Media; D008054:Lipid Peroxides; D003973:Diatrizoate; D012965:Sodium Chloride; D002374:Catalase