L-carnitine prevents increase in diastolic [Ca2+] induced by doxorubicin in cardiac cells

Alfredo Mijares, José R. López

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Doxorubicin is a highly effective anticancer chemotherapeutic agent that produces a dose-dependent cardiomyopathy that limits its clinical usefulness. We investigated the acute effects of doxorubicin on diastolic free Ca2+ concentrations ([Ca2+]) and the cardioprotective action of L-carnitine in isolated cardiomyocytes loaded with fura-2/AM (acetoxymethyl ester). Exposure to 10-6-10-4 M doxorubicin induced an elevation of diastolic calcium concentration ([Ca2+]) that was concentration dependent. Nitrendipine failed to prevent the doxorubicin-induced elevation of [Ca2+]. Incubation with L-carnitine (10-8 to 10-6 M) did not modify [Ca2+]. Pretreatment of cardiomyocytes with L-carnitine 10-8-10-7 M did not prevent the doxorubicin effect on [Ca2+]. However, L-carnitine 10-6 M fully inhibited the increase in [Ca2+] induced by this anthracycline derivative. These results indicate that acute exposure to doxorubicin impairs intracellular Ca2+ handling and that L-carnitine exerts a cardioprotective effect, in part by preventing the doxorubicin-induced increase in diastolic Ca2+ concentration.

Original languageEnglish (US)
Pages (from-to)117-120
Number of pages4
JournalEuropean Journal of Pharmacology
Volume425
Issue number2
DOIs
StatePublished - Aug 10 2001
Externally publishedYes

Fingerprint

Carnitine
Doxorubicin
Cardiac Myocytes
Nitrendipine
Fura-2
Anthracyclines
Cardiomyopathies
Antineoplastic Agents
Esters
Calcium

Keywords

  • Ca
  • Cardiomyocyte
  • Cardioprotection
  • Cardiotoxicity
  • Doxorubicin
  • L-Carnitine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

L-carnitine prevents increase in diastolic [Ca2+] induced by doxorubicin in cardiac cells. / Mijares, Alfredo; López, José R.

In: European Journal of Pharmacology, Vol. 425, No. 2, 10.08.2001, p. 117-120.

Research output: Contribution to journalArticle

Mijares, Alfredo ; López, José R. / L-carnitine prevents increase in diastolic [Ca2+] induced by doxorubicin in cardiac cells. In: European Journal of Pharmacology. 2001 ; Vol. 425, No. 2. pp. 117-120.
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