Effects of a novel low-molecular weight antioxidant on cardiac injury induced by hydrogen peroxide

H290/51, an indenoindole derivative, is a novel low-molecular weight (287.8) inhibitor of lipid peroxidation. Its effect on cardiac injury induced by exogenous reactive oxygen intermediates (ROI) was investigated. ROI were generated by adding H 2O 2 (180 μM) to the perfusate of isolated rat hearts (Langendorff model, n = 9) for 10 min. H 2O 2 reduced left ventricular developed pressure (LVDP = left ventricular systolic pressure - left ventricular end-diastolic pressure) from 90 ± 6 to a minimum of 25 ± 2 mmHg (mean ± SEM) after 10 min ( p < 0.001), elevated left ventricular end-diastolic pressure (LVEDP) from 0 to 32 ± 7 mmHg after 20 min ( p < 0.0001), and increased coronary flow (CF). Lactate dehydrogenase (LDH) release in the coronary effluent and thiobarbituric acid-reactive substances (TBARS) in cardiac tissue increased (TBARS from 0.6 ± 0.04 to 3.1 ± 0.4 nmol/g tissue after 10 min of H 2O 2 administration, p < 0.001). Addition of H290/51 (1 μM, n = 12) from the start of H 2O 2 exposure, attenuated the H 2O 2-induced increase of LVEDP (9 ± 3 mmHg at 20 min, p < 0.006) and reduced the release of LDH ( p < 0.02 at 30 min). LVDP was not significantly influenced. The increase of TBARS was abolished by H290/51 ( p < 0.001). In conclusion, H290/51 inhibited lipid peroxidation, and attenuated functional and biochemical injury induced by H 2O 2 exposure