Cytotoxicity of isoproterenol to cultured heart cells: Effects of antioxidants on modifying membrane damage

Primary cultures of rat myocytes were used to study the cardiac damage induced by toxic doses of l-isoproterenol (ISO). Cultures were exposed to varying concentrations of ISO (2.4 × 10^-5, 1 × 10^-4, and 5 × 10^-4m) for 0.5, 1.5, 4, and 12 hr. Mitochondrial membrane fragility, myocyte potassium content (as an index of sarcolemmal damage), and cellular glutathione content were used to evaluate cellular injury. A significant increase in mitochondrial fragility was observed 0.5 hr after treatment with 5 × 10^-4M ISO. Lower doses caused an increase in mitochondrial fragility 1.5 hr after exposure. Longer durations of ISO exposure (4 and 12 hr) were necessary to decrease cellular potassium content. Glutathione levels were minimally affected by ISO. l-Ascorbic acid (5 × 10^-3m) or sodium bisulfite (9.6 × 10^-4m) were added to the cultures to determine if antioxidants prevent the toxicity caused by ISO. The presence of l-ascorbic acid or sodium bisulfite in ISO-treated myocyte cultures prevented the toxic changes in mitochondrial fragility and myocyte potassium content. The data indicate that antioxidants may be useful in reducing injury induced by toxic doses of ISO. Furthermore, mitochondrial injury may be involved significantly with the development of ISO-induced cardiotoxicity.