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• W2042589623 abstract "<i>Aim:</i> The objective of this study was to examine the interaction ofa 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) with a nitric oxide (NO) donor from the perspective of the impact on cardiomyocyte cell viability. <i>Methods:</i> Embryonic chick cardiomyocytes in culture were treated with a wide range of concentrations of sodium nitroprusside (SNP), which releases NO and also generates toxic reactive nitrogen species. SNP was combined with the HMG-CoA reductase inhibitor lovastatin and cell viability was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. <i>Results:</i> SNP and lovastatin each produced a significant (p < 0.01) concentration-dependent increase in cell death. Using SNP concentrations at or below the ED₅₀, SNP (0.01, 0.1 or 0.5 mmol/l) increased the amount of cell death when combined with lovastatin (1, 10, 50 and 100 µmol/l). At lovastatin concentrations of 50 µmol/l and less, the amount of cell death was consistently similar to the arithmetic sum of SNP and lovastatin, suggesting that there was an additive and not synergistic relationship between SNP and lovastatin. In combination with lovastatin (100 µmol/l), however, the amount of cell death was consistently lower than the calculated expected value and suggested saturation of a common mechanism. The combination of SNP and lovastatin produced the characteristic microscopic changes of apoptosis. Considering that both SNP and lovastatin can activate caspase-3, cells were treated with the caspase-3 inhibitor Ac-DEVD-CHO. This inhibitor produced a significant (p < 0.05) and consistent 30% reduction in the amount of cell death induced by SNP and lovastatin. <i>Conclusion:</i> These data suggest that the cardiomyocyte toxicity from NO continues to be evident uninterrupted by and not accentuated by the presence of an HMG-CoA inhibitor<i>.</i> The cardiac adverse effect of each of these agents utilizes a common pathway involving caspase-3 so that their cardiotoxicity can be blunted by a caspase-3 inhibitor." @default.
• W2042589623 created "2016-06-24" @default.
• W2042589623 creator A5010732739 @default.
• W2042589623 creator A5084294726 @default.
• W2042589623 date "2008-01-01" @default.
• W2042589623 modified "2023-10-16" @default.
• W2042589623 title "Interaction of the HMG-CoA Reductase Inhibitor Lovastatin and Nitric Oxide in Cardiomyocyte Cell Death" @default.
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• W2042589623 doi "https://doi.org/10.1159/000134380" @default.
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• W2042589623 hasPublicationYear "2008" @default.
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