Cardiotoxicity of environmental contaminant tributyltin involves myocyte oxidative stress and abnormal Ca2+ handling

C. L.V. Pereira, C. F. Ximenes, E. Merlo, A. S. Sciortino, J. S. Monteiro, A. Moreira, B. B. Jacobsen, J. B. Graceli, Kenneth S Ginsburg, R. F. Ribeiro Junior, Donald M Bers, I. Stefanon

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Tributyltin (TBT) is an organotin environmental pollutant widely used as an agricultural and wood biocide and in antifouling paints. Countries began restricting TBT use in the 2000s, but their use continues in some agroindustrial processes. We studied the acute effect of TBT on cardiac function by analyzing myocardial contractility and Ca2+ handling. Cardiac contractility was evaluated in isolated papillary muscle and whole heart upon TBT exposure. Isolated ventricular myocytes were used to measure calcium (Ca2+) transients, sarcoplasmic reticulum (SR) Ca2+ content and SR Ca2+ leak (as Ca2+ sparks). Reactive oxygen species (ROS), as superoxide anion (O2•-) was detected at intracellular and mitochondrial myocardium. TBT depressed cardiac contractility and relaxation in papillary muscle and intact whole heart. TBT increased cytosolic, mitochondrial ROS production and decreased mitochondrial membrane potential. In isolated cardiomyocytes TBT decreased both Ca2+ transients and SR Ca2+ content and increased diastolic SR Ca2+ leak. Decay of twitch and caffeine-induced Ca2+ transients were slowed by the presence of TBT. Dantrolene prevented and Tiron limited the reduction in SR Ca2+ content and transients. The environmental contaminant TBT causes cardiotoxicity within minutes, and may be considered hazardous to the mammalian heart. TBT acutely induced a negative inotropic effect in isolated papillary muscle and whole heart, increased arrhythmogenic SR Ca2+ leak leading to reduced SR Ca2+ content and reduced Ca2+ transients. TBT-induced myocardial ROS production, may destabilize the SR Ca2+ release channel RyR2 and reduce SR Ca2+ pump activity as key factors in the TBT-induced negative inotropic and lusitropic effects.

Original languageEnglish (US)
Pages (from-to)371-382
Number of pages12
JournalEnvironmental Pollution
Volume247
DOIs
StatePublished - Apr 1 2019

Keywords

  • Ca signaling
  • Cardiac myocytes
  • Environmental contaminant
  • Metal toxicity
  • Myocardial contractility
  • Organotin
  • Oxidative stress
  • Sparks
  • Tributyltin

ASJC Scopus subject areas

  • Toxicology
  • Pollution
  • Health, Toxicology and Mutagenesis

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    Pereira, C. L. V., Ximenes, C. F., Merlo, E., Sciortino, A. S., Monteiro, J. S., Moreira, A., Jacobsen, B. B., Graceli, J. B., Ginsburg, K. S., Ribeiro Junior, R. F., Bers, D. M., & Stefanon, I. (2019). Cardiotoxicity of environmental contaminant tributyltin involves myocyte oxidative stress and abnormal Ca2+ handling. Environmental Pollution, 247, 371-382. https://doi.org/10.1016/j.envpol.2019.01.053