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Antimony induces oxidative stress in cultured cardiac myocytes.
Toraason-M; Tirmenstein-MA; Plews-PI; Walker-CV; Woolery-MD; Wey-HE
Toxicologist 1994 Mar; 14(1):169
Potassium antimony tartrate (PAT) is cardiotoxic in man and experimental animals, although the mechanism of action is unknown. The present study investigated the effect of PAT on cultured cardiac myocytes. Spontaneously beating cardiac myocytes were exposed to 1-1000 uM PAT for 1-24 hr. PAT produced a concentration- and time-dependent depression in chronotropy and an increase in the release of both lactate dehydrogenase (LDH) and lipid peroxidation products (TBARS). A 4 hr exposure to 10 uM PAT significantly reduced chronotropy. A 4 hr exposure to 100 uM PAT stopped beating and induced significant increases in TBARS and LDH release. The lipid peroxidation and cell death induced by 100 uM PAT were prevented at 4 hrs by an 18 hr pretreatment of the cardiac myocytes with vitamin E, or by simultaneous treatment with N,N'-diphenyl-p-phenylenediamine. These antioxidants prevented lipid peroxidation for up to 18 hr after the addition of 100 uM PAT, but failed to protect against cell death. 100 uM PAT produced a significant reduction in cardiac myocyte glutathione (GSH) levels after a 4 hr exposure. This reduction was not accompanied by measurable increases in cellular levels of oxidized glutathione. Simultaneous treatment of myocytes with the thiol containing compounds dithiothreitol, GSH' or 2mercaptoethaonol offered limited protection against lipid peroxidation and cell death up to 18 hr after the addition of 100 11M PAT. These results suggest that PAT induces lipid peroxidation in cultured cardiac myocytes, but that other mechanisms may be responsible for toxicity. Results also suggest that PAT interacts with thiol containing compounds.
Laboratory-testing; Toxins; Toxicology; Toxic-effects; Antimony-compounds; Cardiac-function; Cardiovascular-function; Exposure-assessment; Exposure-levels; Myocardial-disorders
Issue of Publication
The Toxicologist. Society of Toxicology 33rd Annual Meeting, March 13-17, 1994, Dallas, Texas