Modifying intracellular redox balance: an approach to improving therapeutic index.

It was postulated that the therapeutic index of very toxic, oxidative drugs could be improved by concurrent treatment with other agents, such as methylene-blue, which affect the concentration of intracellular reducing agents. In support of this hypothesis, methylene-blue was found to protect mice against the toxic effects of doxorubicin without reducing doxorubicin's antineoplastic activity. Because the clinical usefulness of doxorubicin, the most commonly used and broadly active chemotherapeutic agent, is severely limited by acute and cumulative toxic effects, clinical trials of the effect of methylene-blue on the toxic therapeutic ratio of doxorubicin and other oxidative quinone drugs should be considered.