Antimony-induced alterations in thiol homeostasis and adenine nucleotide status in cultured cardiac myocytes.

Cultured cardiac myocytes were exposed for up to 4 h to 50 and 100 microM potassium antimonyl tartrate (PAT). After 4 h, 50 and 100 microM PAT killed 14 and 33% respectively of the cardiac myocytes. PAT-induced alterations in both protein and nonprotein thiol homeostasis. Transient increases in oxidized glutathione disulfide (GSSG) levels were detected after cells were treated with 100 microM PAT for 2 h. After 4 h, both concentrations of PAT significantly depleted reduced glutathione (GSH) levels. Protein thiols levels were also decreased after a 2-h exposure to 50 and 100 microM PAT. Cells treated with 50 microM and 100 microM PAT had a 15% and 40% reduction respectively in protein thiols after 4 h. PAT also significantly inhibited glutathione peroxidase and pyruvate dehydrogenase activity in cardiac myocytes. Pyruvate dehydrogenase activity levels were inhibited as early as 1 h after cells were treated with both concentrations of PAT. Cardiac myocyte ATP levels were also decreased by PAT, but only after a 4-h exposure to 50 microM and 100 microM PAT. Decreases in cellular ATP levels paralleled PAT toxicity put appeared to be secondary to other cellular changes initiated by PAT exposure.