Sk. Nelson et al., THE TOXICITY OF HIGH-DOSE SUPEROXIDE-DISMUTASE SUGGESTS THAT SUPEROXIDE CAN BOTH INITIATE AND TERMINATE LIPID-PEROXIDATION IN THE REPERFUSED HEART, Free radical biology & medicine, 16(2), 1994, pp. 195-200
Recently, we described an anomalous bell-shaped dose-response curve fo
r the protection of the reoxygenated isolated myocardium by superoxide
dismutase (SOD). (SOD)-S-19 is dramatically protective up to a point
(5 mu/ml in the perfusate) beyond which it loses its ability to protec
t and, at very high doses (50 mu g/ml), exacerbates the injury. We pro
posed that O-2.(-) may serve as both initiator and terminator of lipid
peroxidation, such that over scavenging the radical may increase net
lipid peroxidation via increased chain length. We examined the ability
of U74389F, a lipid peroxidation inhibitor, to ameliorate the toxicit
y of high-dose SOD in the isolated perfused rabbit heart preparation.
The results show a significant improvement in the percent recovery of
developed tension of hearts treated with U74389F and overdosed with Mn
SOD, as well as a decrease in thiobarbituric acid reactive substances.