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

• Published in: Toxicology (Amsterdam) Vol. 119; no. 3; pp. 203 - 211
• Main Authors: Tirmenstein, M.A., Mathias, P.I., Snawder, J.E., Wey, H.E., Toraason, M.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 16.05.1997; Amsterdam Elsevier Science
• Subjects: Adenine nucleotides; Adenine Nucleotides - metabolism; Animals; Antimony; Antimony Potassium Tartrate - toxicity; Biological and medical sciences; Cardiac myocytes; Cell Survival - drug effects; Cells, Cultured; Chemical and industrial products toxicology. Toxic occupational diseases; Glutathione; Glutathione - analogs & derivatives; Glutathione - metabolism; Glutathione Disulfide; Heart - drug effects; L-Lactate Dehydrogenase - metabolism; Medical sciences; Metals and various inorganic compounds; Myocardium - cytology; Myocardium - metabolism; Oxidative Stress - drug effects; Oxidoreductases - metabolism; Pyruvate dehydrogenase; Pyruvate Dehydrogenase Complex - metabolism; Rats; Rats, Sprague-Dawley; Schistosomicides - toxicity; Thiol; Toxicology; Antimony; Pyruvate dehydrogenase; Thiol; Cardiac myocytes; Adenine nucleotides; Glutathione; Heart; Cell culture; Rat; Toxicity; Rodentia; In vitro; Site of action; Myocyte; Vertebrata; Mammalia; Heart disease; Animal; Mechanism of action; ATP
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(97)03628-7

Cultured cardiac myocytes were exposed for up to 4 h to 50 and 100 μM potassium antimonyl tartrate (PAT). After 4 h, 50 and 100 μM 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 μM 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 μM PAT. Cells treated with 50 μM and 100 μM 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 μM and 100 μM PAT. Decreases in cellular ATP levels paralleled PAT toxicity put appeared to be secondary to other cellular changes initiated by PAT exposure.