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Overexpression of thioredoxin-1 in transgenic mice attenuates adriamycin-induced cardiotoxicity

Keisuke Shioji1, Chiharu Kishimoto, Hajime Nakamura

  • 1Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan.

Circulation
|September 11, 2002
PubMed
Abstract

Insights

Thioredoxin-1 (TRX1) combats Adriamycin (ADR)-induced heart damage by reducing oxidative stress. This redox-regulating molecule shows protective effects against ADR cardiotoxicity in both cell cultures and animal models.

Area of Science:

  • Biochemistry
  • Cardiology
  • Molecular Biology

Background:

  • Adriamycin (ADR) is an effective anticancer drug.
  • ADR treatment can lead to severe cardiotoxicity due to free radical generation.
  • Thioredoxin-1 (TRX1) is a key redox-regulating molecule.

Purpose of the Study:

  • To investigate the role of thioredoxin-1 (TRX1) in Adriamycin (ADR)-induced cardiotoxicity.
  • To determine if TRX1 can mitigate ADR-induced cardiac damage.

Main Methods:

  • In vitro studies using neonatal rat cardiomyocytes treated with ADR and recombinant human TRX1.
  • In vivo studies using transgenic mice overexpressing TRX1 (TRX1-TG) and wild-type (WT) mice treated with ADR.
  • Assessment of cardiomyocyte injury, cellular structure via electron microscopy, protein oxidation markers, hydroxyl radical formation, and survival rates.

Main Results:

  • TRX1 expression increased with hydroxyl radical formation in ADR-treated cardiomyocytes.
  • Recombinant TRX1 protected cardiomyocytes from ADR-induced injury in vitro.
  • TRX1-TG mice showed better preservation of cellular structures and reduced protein oxidation compared to WT mice after ADR treatment.
  • TRX1-TG mice exhibited decreased hydroxyl radical formation and significantly improved survival rates following ADR administration.

Conclusions:

  • Adriamycin induces intracellular oxidative stress, leading to upregulation of TRX1.
  • TRX1 plays a significant protective role against Adriamycin-induced cardiotoxicity by mitigating oxidative stress.

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