Evidence has accumulated for a role of toxic
oxygen radicals in the pathogenesis of
ischemia-reperfusion injury in the kidney. The aim of this study was to evaluate the hypothesis that reducing postischemic renal injury is possible by delivery of the gene for the
antioxidant enzyme superoxide dismutase (SOD). Female Sprague-Dawley rats received
intravenous injections of recombinant adenovirus (1 x 10(9) pfu) containing the transgenes for Escherichia coli
beta-galactosidase (Ad-LacZ, as control) or human Cu/Zn-SOD (Ad-SOD). Three days later, renal
ischemia was produced by cross-clamping the left renal vessels for 60 min. The right kidney was removed before reperfusion and processed for the transgene. Renal SOD
protein and activity in rats given Ad-SOD was 2.5-fold higher than from the animals receiving Ad-LACZ: Urinary
lactate dehydrogenase concentrations were elevated by
ischemia-reperfusion in the Ad-LacZ group (1403 +/- 112 U/L), yet values were 50% lower in Ad-SOD-treated rats.
Free radical production was elevated by
ischemia-reperfusion but was significantly lower in SOD-treated animals. Importantly, on postischemic day 1, glomerular filtration rates were reduced to 0.21 ml/min per 100 g in the Ad-LacZ group, whereas values remained significantly higher (0.39) in the Ad-SOD group. Two weeks after
ischemia-reperfusion,
inflammation, interstitial
fibrosis, tubular
atrophy and tissue levels of
tumor necrosis factor alpha and
interleukin-1 were significantly higher in the Ad-LacZ-treated than in Ad-SOD-treated rats. In conclusion, these results indicate that SOD expression can be increased by delivery of the sod gene to the kidney by
intravenous injection and that sod gene transduction minimized
ischemia-reperfusion-induced
acute renal failure.