Antimony Induces Oxidative Stress in Cultured Cardiac Myocytes

Details

• Personal Author:
  Plews PI ; Tirmenstein MA ; Toraason M ; Walker CV ; Wey HE ; Woolery MD
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Antimony Cardiovascular System Environmental Monitoring Hazardous Substances Laboratories Occupational Health Safety Toxicology
• Keywords:
  Antimony-compounds Cardiac-function Cardiovascular-function Exposure-assessment Exposure-levels Laboratory-testing Myocardial-disorders Toxic-effects Toxins
• ISSN:
  0731-9193
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Ohio ; 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:
  14
• Issue:
  1
• NIOSHTIC Number:
  nn:20035546
• Citation:
  Toxicologist 1994 Mar; 14(1):169
• CAS Registry Number:
  Antimony (CAS RN 7440-36-0)
• Federal Fiscal Year:
  1994
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 33rd Annual Meeting, March 13-17, 1994, Dallas, Texas
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0bb996ab3ed06b10451e04c934d5566c564a93e76df168fa1e2c89cba799378f9dab27937c3307bb55e6128a2fda94cfa680fbe3378d5bc0c9f80c2c58f8f11a
• Download URL:
  https://stacks.cdc.gov/view/cdc/187370/cdc_187370_DS1.pdf
• File Type:
  [PDF - 231.77 KB ]