Doxorubicin interacts directly with skinned single skeletal muscle fibres

Eur J Pharmacol. 1992 Apr 7;214(1):97-100. doi: 10.1016/0014-2999(92)90103-b.

Abstract

The effect of doxorubicin, a highly effective anticancer agent, on the contractile apparatus of skinned single muscle fibres was tested in a concentration of 1 microM. Sarcomere length was set and held at 2 microns. Doxorubicin induced an increase in tension dependent on the Ca2+ concentration and time of incubation. The rise was up to 25% at [Ca2+] 40 microM. A parallel, small but significant shift of the calcium sensitivity curve, the relation between normalized tension and the negative logarithm of [Ca2+], the pCa, was observed. The results of this study suggest a direct interaction of doxorubicin with the actin myosin structure, possibly by an effect on myosin-ATP activity.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cyclic N-Oxides / pharmacology
  • Doxorubicin / pharmacology*
  • Free Radicals
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Muscles / drug effects*
  • Rabbits

Substances

  • Cyclic N-Oxides
  • Free Radicals
  • Doxorubicin
  • Calcium
  • TEMPO