Inhibition of cardiac guanylate cyclase by doxorubicin and some of its analogs

Abstract

Doxorubicin, an anthracycline antibiotic and antitumor agent, has cardiotoxic side-effects that limit its therapeutic usefulness. We have demonstrated that the drug inhibits cardiac guanylate cyclase activity in vitro. The biochemical changes following anthracycline treatment are described, and the various hypotheses attempting to account for cardiotoxicity in terms of a molecular mechanism are reviewed. It is suggested that inhibition of cardiac guanylate cyclase activity may be a consequence of the increase in free radicals and oxidative damage following treatment with doxorubicin or related compounds.