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Effects of a novel low-molecular weight antioxidant on cardiac injury induced by hydrogen peroxide
Abstract:
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 H2O2 (180 mu M) to the perfusate of isolated rat hearts (Langendorff model, n = 9) for 10 min. H2O2 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 H2O2 administration, p < 0.001). Addition of H290/51 (1 mu M, n = 12) from the start of H2O2 exposure, attenuated the H2O2-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 H2O2 exposure.
Insights
H290/51, a novel lipid peroxidation inhibitor, protected isolated rat hearts from hydrogen peroxide (H2O2) induced injury. This compound reduced cardiac dysfunction and biochemical markers of oxidative stress.
Area of Science:
- Cardiovascular Research
- Oxidative Stress Biology
- Pharmacology
Background:
- Reactive oxygen intermediates (ROI) cause cardiac injury.
- Lipid peroxidation is a key mechanism in ROI-induced cardiac damage.
- Novel inhibitors are needed to mitigate oxidative stress in the heart.
Purpose of the Study:
- To investigate the protective effects of H290/51, a novel lipid peroxidation inhibitor, against exogenous ROI-induced cardiac injury.
- To assess the impact of H290/51 on functional and biochemical markers of cardiac damage.
Main Methods:
- Isolated rat hearts (Langendorff model) were exposed to hydrogen peroxide (H2O2) to induce oxidative stress.
- Cardiac function (LVDP, LVEDP, CF) and biochemical markers (LDH, TBARS) were measured.
- The effect of H290/51 (1 μM) on H2O2-induced injury was evaluated.
Main Results:
- H2O2 significantly reduced left ventricular developed pressure (LVDP), increased left ventricular end-diastolic pressure (LVEDP), and elevated coronary flow.
- H2O2 exposure increased lactate dehydrogenase (LDH) release and cardiac thiobarbituric acid-reactive substances (TBARS).
- H290/51 attenuated the increase in LVEDP and LDH release, and completely abolished the rise in TBARS, without significantly affecting LVDP.
Conclusions:
- H290/51 effectively inhibits lipid peroxidation.
- H290/51 demonstrates cardioprotective effects by attenuating functional and biochemical damage induced by H2O2.
- This indenoindole derivative shows potential as a therapeutic agent against oxidative stress-related cardiac injury.