Renal
ischemia-reperfusion injury constitutes the most common pathogenic factor for
acute renal failure and is the main contributor to renal dysfunction in allograft recipients and revascularization surgeries. Many studies have demonstrated that
reactive oxygen species play an important role in ischemic
acute renal failure. The aim of the present study was to investigate the effects of the synthetic
antioxidant U-74500A, a 21-aminosteroid in a rat model of renal
ischemia-reperfusion injury. Renal
ischemia-reperfusion was induced by clamping unilateral renal artery for 45 min followed by 24 h of reperfusion. Two doses of
U-74500A (4.0 mg/kg, i.v.) were administered 45 min prior to renal artery occlusion and then 15 min prior to reperfusion. Tissue lipid peroxidation was measured as
thiobarbituric acid reacting substances (
TBARS) in kidney homogenates. Renal function was assessed by estimating serum
creatinine, blood
urea nitrogen (BUN),
creatinine and
urea clearance. Renal morphological alterations were assessed by histopathological examination of
hematoxylin-
eosin stained sections of the kidneys.
Ischemia-reperfusion produced elevated levels of
TBARS and deteriorated the renal function as assessed by increased serum
creatinine, BUN and decreased
creatinine and
urea clearance as compared to
sham operated rats. The ischemic kidneys of rats showed severe hyaline casts, epithelial swelling, proteinaceous debris, tubular
necrosis, medullary congestion and
hemorrhage.
U-74500A markedly attenuated elevated levels of
TBARS as well as morphological changes, but did not improve renal dysfunction in rats subjected to renal
ischemia-reperfusion. These results clearly demonstrate the in vivo
antioxidant effect of
U-74500A, a 21-aminosteroid in attenuating renal
ischemia-reperfusion injury.