Role of Calcium and Phospholipase in Potassium Antimonyl Tartrate-Induced Cardiac Myocyte Toxicity

Details

• Personal Author:
  Mathias P ; Richards D ; Tirmenstein M ; Toraason M ; Walker C ; Wey H
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Calcium Compounds Environmental Monitoring Laboratories Occupational Health Safety
• Keywords:
  Animal-studies Calcium-compounds Cellular-reactions Exposure-assessment Exposure-limits Laboratory-animals
• ISSN:
  0731-9193
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  North Carolina ; Ohio ; OSHA Region 4 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DBBS - Division of Biomedical and Behavioral Sciences
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  15
• Issue:
  1
• NIOSHTIC Number:
  nn:20032258
• Citation:
  Toxicologist 1995 Mar; 15(1):310
• CAS Registry Number:
  Calcium (CAS RN 7440-70-2)
• Federal Fiscal Year:
  1995
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 34th Annual Meeting, March 5-9,1995, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:12806b69fb5863be6b7ca2abb1ad83f0a2b32b5a3358c666d386c84a6563213d87bdc19769f730c674ae6b2fca04ffc4e8f01b1d3fe15b4c36dc02ff861a4487
• Download URL:
  https://stacks.cdc.gov/view/cdc/186289/cdc_186289_DS1.pdf
• File Type:
  [PDF - 940.42 KB ]