Thermal preconditioning protects rat cardiac muscle cells from doxorubicin-induced apoptosis

Life Sci. 1999;64(9):755-61. doi: 10.1016/s0024-3205(98)00617-1.


Doxorubicin (DOX=adriamycine), an effective chemotherapeutic agents for cancers, has severe cardiotoxicity. In the paresent study, we examined the protective effect of thermal preconditioning (TP) against apoptosis of rat cardiac muscle cells induced by DOX. Treatment with DOX (10 microM) for 24 hrs resulted in apoptosis of cardiac muscle cells, which was evaluated by examining "DNA ladder" formation and TUNEL staining. The number of TUNEL-positive cells was significantly decreased in cells subjected to TP by incubation at 42 degrees C for 30 min, 24 hrs prior to DOX-treatment. Antisense oligonucleotides of the heat shock protein (HSP) 70 blunted this effect. These results indicate that DOX-induced apoptosis in cardiac muscle cells is prevented by TP, at least in part, via a HSP70-mediated mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antineoplastic Agents / toxicity*
  • Apoptosis* / drug effects
  • Cells, Cultured
  • DNA / analysis
  • DNA Damage / drug effects
  • DNA Damage / genetics
  • DNA, Complementary / analysis
  • Doxorubicin / toxicity*
  • Electrophoresis, Agar Gel
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heart / drug effects*
  • Hot Temperature
  • Hyperthermia, Induced*
  • In Situ Nick-End Labeling
  • Ischemic Preconditioning, Myocardial
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Oligonucleotides, Antisense / pharmacology
  • Rats


  • Antineoplastic Agents
  • DNA, Complementary
  • HSP70 Heat-Shock Proteins
  • Oligonucleotides, Antisense
  • Doxorubicin
  • DNA