Antimony-induced oxidative stress and toxicity in cultured cardiac myocytes.
Cardiac myocytes were exposed to concentrations of potassium antimonyl tartrate (PAT) ranging from 1 to 1000 microM for 1 to 24 hr. Toxicity was assessed by measuring lactate dehydrogenase (LDH) release and by monitoring chronotropic depression. Lipid peroxidation was assessed by measuring the release of thiobarbituric acid reactive substances (TBARS). PAT produced a concentration- and time-dependent depression in chronotropy and an increase in the release of LDH and TBARS. A 4-hr exposure to 100 microM PAT stopped beating and induced significant increases in TBARS and LDH release in the myocyte cultures. The lipid peroxidation and LDH release induced by 100-200 microM PAT at 4 hr could be prevented by pretreatment of the cardiac myocytes with vitamin E or by the simultaneous addition of other antioxidants. Vitamin E continued to protect against lipid peroxidation up to 18 hr after the addition of 100 microM PAT, but failed to provide significant protection against LDH release at this time-point. Both 50 and 100 microM PAT decreased cardiac myocyte glutathione (GSH) levels after a 4-hr exposure. A series of thiol-containing compounds was evaluated for their effects on PAT toxicity. The addition of dithiothreitol, GSH, and 2-mercaptoethanol afforded some degree of protection against lipid peroxidation and LDH release up to 18 hr after the addition of 100 microM PAT. These results suggest that PAT induces lipid peroxidation in cultured cardiac myocytes but that other mechanisms may contribute to cell death with long-term exposures to PAT. Our results also suggest that PAT interacts with thiol-containing compounds.
Tirmenstein
M A
MA
Cellular Toxicology Section, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, Ohio.
Plews
P I
PI
Walker
C V
CV
Woolery
M D
MD
Wey
H E
HE
Toraason
M A
MA
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000966:Antimony Potassium Tartrate / Q000008:administration & dosage / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008623:Mercaptoethanol / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000201:enzymology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D008623:Mercaptoethanol; D000966:Antimony Potassium Tartrate; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D004229:Dithiothreitol