The effect of a new synthetic
superoxide dismutase and
catalase mimetic was investigated on renal
ischemia-reperfusion syndrome in rats. Synthetic
salen-
manganese complexes have characteristics that might facilitate their potential usefulness as therapeutic agents: (1) unlike proteinaceous
antioxidant enzymes, synthetic complexes, due to their low molecular weight, have a better stability and bioavailability; (2) they have a catalytic activity enhancing their efficiency over noncatalytic reactive
oxygen metabolite scavengers; and finally, (3) exhibiting combined
superoxide dismutase and
catalase activity, they destroy both
superoxide anions and
hydrogen peroxides, thereby enhancing their protective effect on ischemically injured tissues. One such compound,
EUK-134, was tested in uninephrectomized rats that underwent a left renal artery clamping. After a 75-min left renal artery clamping, a single
intravenous injection of
EUK-134 at 0.2 mg/kg, just before unclamping, provided significantly better renal function recovery during the week after the ischemic insult compared with recovery of untreated animals. Two hours after several periods of renal
ischemia (30, 45, 60, and 75 min of left renal artery clamping),
EUK-134 given at a similar dose significantly improved the glomerular filtration rate after an acute
ischemia of 30 and 45 min, as assessed by
EDTA 51Cr. Overall, these results show that synthetic
superoxide dismutase-
catalase mimetics such as
EUK-134 can protect ischemically injured rat kidneys from
ischemia-reperfusion syndrome when administered just before reperfusion.