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Role of calcium and phospholipase in potassium antimonyl tartrate-induced cardiac myocyte toxicity.

Authors
Wey-H; Richards-D; Mathias-P; Tirmenstein-M; Walker-C; Toraason-M
Source
Toxicologist 1995 Mar; 15(1):310
NIOSHTIC No.
20032258
Abstract
Exposure of rat cardiac myocytes to potassium antimonyl tartrate (PAT) has been shown to cause oxidative stress and toxicity. This study investigates the roles of intracellular calcium (Ca2+i) and phospholipase (PLPase) activation in PAT-induced toxicity. Myocytes isolated from rat neonates were cultured on plastic culture dishes or glass coverslips and were used after 2-3 days in culture. Toxicity and lipid peroxidation were assessed by release of lactate dehydrogenase (LDH) and thiobarbituric acid reactive substances (TBARS), respectively. Ca2+i was monitored on an inverted phase contrast microscope with the fluorescent probe fura-2. ATP content was measured by extraction and HPLC analysis. Exposure to 200 JLM PAT for 4 hrs resulted in a 50-60% release of LDH (% of total) and a 10-fold increase in TBARS release. In individual fura-2 loaded myocytes, 200 JLM PAT increased Ca2+i by approximately 75% by3 hours, whereas, exposure to 500 JLM PAT resulted in Ca2+i overload (greater than 10-fold increase). Preloading of myocytes with the Ca2+ chelator BAPTA (10 JLM) prevented the effects of PAT on LDH and TBARS release, but PAT exposure in calcium-free/EGTA medium did not prevent toxicity, suggesting release from intracellular Ca2+ stores. Co-exposure to the PLPase inhibitor mepacrine also prevented PAT toxicity. After 6 hrs exposure to PAT (200 JLM) in the presence of mepacrine (50 JLM) LDH release was still prevented, but myocytes were hypercontracted, suggesting an elevated Ca2+i. PAT-induced ATP loss was partially prevented by BAPTA and mepacrine. These results link elevated Ca2+i and activation of PLPase with PAT-induced myocyte cell death and suggest that increased Ca2+i precedes phospholipase activation.
Keywords
Exposure-assessment; Exposure-limits; Cellular-reactions; Animal-studies; Laboratory-animals; Calcium-compounds
CAS No.
7440-70-2
Publication Date
19950301
Document Type
Abstract
Fiscal Year
1995
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0731-9193
NIOSH Division
DBBS
Source Name
The Toxicologist. Society of Toxicology 34th Annual Meeting, March 5-9,1995, Baltimore, Maryland
State
OH; NC
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