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Antimony-induced oxidative stress and toxicity in cultured cardiac myocytes.
Tirmenstein-MA; Plews-PI; Walker-CV; Woolery-MD; Wey-HE; Toraason-MA
Toxicol Appl Pharmacol 1995 Jan; 130(1):41-47
As part of an effort to elucidate the toxicological mechanisms of antimony (7440360), a study was conducted to assess the effects of potassium-antimonyl-tartrate (28300745) (PAT) on neonatal rat cardiac myocytes. Cardiac ventricle cells were isolated from neonatal Sprague-Dawley-rats and, following treatment to separate fibroblasts from myoblasts, plated at a density of 1,000,000 cells per 35 millimeter (mm) well. After 48 hours (hr), cultures were subjected to lipid peroxidation and cytotoxicity analyses and then washed with a salt solution and exposed to 2 milliliter aliquots of PAT in serum free M199 media for 4hr. Antioxidants and compounds containing thiol were added along with the PAT. At the end of the exposure period, the cultures were analyzed for the presence and level of thiobarbituric-acid reactive substances (TBARS) release and lactate-dehydrogenase (LDH) leakage for an assessment of toxicity. Glutathione levels and myocyte spontaneous beating rate were also determined. Exposure durations of greater than 1hr were required for appreciable toxicity to occur. TBARS production was seen to parallel LDH release at 4 and 18h. The extent of toxicity was correlated with the length of PAT exposure. Pretreatment of cultures with vitamin-E inhibited TBARS production and LDH release. Deferoxamine, dithiothreitol, N-N'-diphenyl-p-phenylenediamine and chlorpromazine also showed inhibitory effects on TBARS and LDH release. The authors conclude that PAT is toxic to cardiac myocytes and is capable of inducing a state of oxidative stress, and that antioxidants and thiol containing compounds confer a degree of protection to cells.
NIOSH-Author; Heavy-metals; Toxicology; Sulfur-compounds; Enzymatic-effects; Mammalian-cells; Cell-cultures; In-vitro-studies; Oxidative-processes
Issue of Publication
Toxicology and Applied Pharmacology
Page last reviewed: April 12, 2019
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