Hypoperfusion-induced acute renal failure in the rat: an evaluation of oxidant tissue injury.
Reactive oxygen species (ROS) have been reported to be critical cellular mediators of experimental ischemic acute renal failure (ARF). This conclusion is based on observations that in the renal artery occlusion (RAO) model of ARF, antioxidant drugs confer protection and that renal malondialdehyde (MDA) concentrations, an index of lipid peroxidation, rise in the postischemic period. Human ischemic ARF is most often due to hypoperfusion, not to total blood flow interruption. Therefore, the goal of this study was to determine whether ROS also mediate hypoperfusion-induced renal injury. Renal hypoperfusion was induced in rats by suprarenal partial aortic ligation, lowering renal perfusion pressure to 20-25 mm Hg for 45 minutes. Renal MDA concentrations were measured 15 minutes after ligation release. Renal function and morphology were assessed 24 hours after hypoperfusion in control rats and in rats pretreated with antioxidant agents (allopurinol, superoxide dismutase, dimethyl-thiourea, glutathione, and catalase), a majority of which have been shown to lessen RAO-induced ARF. Hypoperfusion caused no rise in renal MDA concentrations (p = 0.54). Control ARF rats developed significant azotemia (blood urea nitrogen 119 +/- 6 mg/dl; creatinine 3.3 +/- 0.37 mg/dl) and widespread tubular necrosis by 24 hours after surgery. None of the antioxidants, administered singly or in combination, lessened the ischemic damage. Therefore, renal MDA concentrations do not rise in hypoperfusion ARF, and antioxidants do not confer protection. This indicates that previous evidence for ROS as mediators of ischemic renal injury is restricted to the RAO model of ARF, which does not closely simulate most human ischemic renal injury.
D058186:Acute Kidney Injury / Q000209:etiology* / Q000517:prevention & control; D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002374:Catalase / Q000627:therapeutic use; D005260:Female; D005978:Glutathione / Q000627:therapeutic use; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D013482:Superoxide Dismutase / Q000627:therapeutic use; D013890:Thiourea / Q000031:analogs & derivatives / Q000627:therapeutic use
D000975:Antioxidants; D008315:Malondialdehyde; D000493:Allopurinol; C038983:1,3-dimethylthiourea; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D013890:Thiourea