Inhibition of doxorubicin-induced injury in the catalase overexpressing heart of transgenic mice

Y. Chen, Yujian Kang

Research output: Contribution to journalArticle

Abstract

Heart injury is a major limiting factor for clinical application of doxorubicin in cancer chemotherapy. This cardiac damage is mediated at least in part by reactive oxygen free radicals produced during the drug metabolism. However, studies in attempts to decrease doxorubicin cardiotoxicity by supplementation of antioxidants such as Superoxide dismutase and catalase are controversial. This controversy likely results from unpredicted tissue distribution and cellular exclusion of these antioxidants. To overcome these obstacles, we produced transgenic mice in which catalase is specifically overexpressed in the heart. Using this unique experimental model we determined the role of catalase in cardioprotection against doxorubicin toxicity. Transgenic mice with elevated cardiac catalase activity 50-fold higher than normal, together with non-transgenic controls, were treated with doxorubicin by ip at 20 mg/kg. Hour days after the treatment, lipid peroxide contents (estimated by malondialdehyde concentration) in the heart and serum creatine phosphokinase activity were determined. Catalase overexpression very markedly suppressed these doxorubicin-induced cardiac injuries. In addition, isolated atria were used to determine the effect of catalase on doxorubicin-induced functional changes in vitro. Elevation of catalase activity inhibited doxorubicin-reduced inotropy in the left atrium and chronotropy in the right atrium. The results provide direct support for free radical hypothesis of doxorubicininduced cardiotoxicitv and demonstrate the importance of catalase in the cardioprotection.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996
Externally publishedYes

Fingerprint

doxorubicin
Catalase
Doxorubicin
Transgenic Mice
catalase
heart
genetically modified organisms
mice
Wounds and Injuries
Heart Atria
Free Radicals
Antioxidants
Heart Injuries
antioxidants
Chemotherapy
Lipid Peroxides
tissue distribution
creatine kinase
Tissue Distribution
Creatine Kinase

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Inhibition of doxorubicin-induced injury in the catalase overexpressing heart of transgenic mice. / Chen, Y.; Kang, Yujian.

In: FASEB Journal, Vol. 10, No. 3, 01.12.1996.

Research output: Contribution to journalArticle

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