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. Catalase-treated WD rats did not experience renal dysfunction and enhanced lipid peroxidation by DTZ, while heat-inactivated catalase or low dose catalase (0.14 mg x 2 days) failed to prevent DTZ-induced renal dysfunction. Thus, in volume depletion, in which local antioxidant levels are depressed, DTZ induced oxidant-mediated prolonged renal dysfunction and lipid peroxidation.