Increasing therapeutic effect and reducing toxicity of doxorubicin by N-acyl dehydroalanines.
(1989) European Journal of Cancer and Clinical Oncology — Vol. 25, n° 4, p. 679-685 (1989)
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- Abstract
- Doxorubicin toxicity is generally accepted to be free radical-mediated. N-Substituted dehydroalanines (indexed as AD compounds) are capto-dative olefins which react and scavenge free radicals, especially the superoxide anion (O2-) and hydroxyl radical (HO). AD-20, an orthomethoxyphenylacetyl dehydroalanine derivative, decreases the mortality of mice when administered before an acute single dose or multiple non-toxic doses of doxorubicin. Doxorubicin administered to mice induces elevated serum transaminase levels, and the pretreatment of mice with AD-20 decreases significantly these serum enzymatic activities. Preliminary histological examinations suggest that these serum transaminase elevations reflect most likely liver injury. In addition to its cardiotoxicity, doxorubicin induces a severe bone marrow depletion. Although this initial decrease in the peripheral leukocytes induced by doxorubicin is not prevented by the administration of AD-20, it produces a fast recuperation in the white blood cells levels after 1 week, supporting a protective effect at this level. Moreover, the antitumor effect of doxorubicin in L1210 tumor-bearing mice was enhanced when AD-20 was injected before doxorubicin. We postulate that these effects may be related to the free radical scavenging ability of AD-20.
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Buc Calderon, P., Praet, M., Ruysschaert, J. M., & Roberfroid, M. (1989). Increasing therapeutic effect and reducing toxicity of doxorubicin by N-acyl dehydroalanines. European Journal of Cancer and Clinical Oncology, 25(4), 679-685. https://doi.org/10.1016/0277-5379(89)90204-6 (Original work published 1989)