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.
Tirmenstein
M A
MA
Division of Biomedical and Behavioral Science, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, OH 45226, USA.
Mathias
P I
PI
Snawder
J E
JE
Wey
H E
HE
Toraason
M
M
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D000966:Antimony Potassium Tartrate / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D006321:Heart / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012556:Schistosomicides / Q000633:toxicity*
D000227:Adenine Nucleotides; D011768:Pyruvate Dehydrogenase Complex; D012556:Schistosomicides; D000966:Antimony Potassium Tartrate; D010088:Oxidoreductases; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D019803:Glutathione Disulfide