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7-monohydroxyethylrutoside protects against chronic doxorubicin-induced cardiotoxicity when administered only once per week.
Clin Cancer Res 2000; 6(4):1337-41CC

Abstract

Doxorubicin is a very effective antitumor agent, but its clinical use is limited by the occurrence of a cumulative dose-related cardiotoxicity, resulting in congestive heart failure. 7-Monohydroxyethylrutoside (monoHER), a flavonoid belonging to the semisynthetic hydroxyethylrutoside family, has been shown to protect against doxorubicin-induced cardiotoxicity when administered i.p. at a dose of 500 mg/kg five times/week in combination with a weekly i.v. dose of doxorubicin. Such a dosing schedule would be very inconvenient in clinical practice. We therefore investigated a dosing schedule of one administration of monoHER just before doxorubicin. The electrocardiogram was measured telemetrically in mice after the combined treatment of doxorubicin (4 mg/kg, i.v.) with one dose of monoHER (500 mg/kg, i.p., administered 1 h before doxorubicin) for 6 weeks. These data were compared with the five times/week schedule (500 mg/kg, i.p., administered 1 h before doxorubicin and every 24 h for 4 days). The increase of the ST interval was used as a measure for cardiotoxicity. It was shown that 500 mg/kg monoHER administered only 1 h before doxorubicin provided complete protection against the cardiotoxicity. This protection was present for at least 10 weeks after the last treatment. Because of the short half-life of monoHER, these results suggest that the presence of monoHER is only necessary during the highest plasma levels of doxorubicin.

Authors+Show Affiliations

Department of Medical Oncology, University Hospital Vrye Universiteit, Amsterdam, The Netherlands. f.vanacker.azvu.nl.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10778960

Citation

van Acker, F A., et al. "7-monohydroxyethylrutoside Protects Against Chronic Doxorubicin-induced Cardiotoxicity when Administered Only once Per Week." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 6, no. 4, 2000, pp. 1337-41.
van Acker FA, van Acker SA, Kramer K, et al. 7-monohydroxyethylrutoside protects against chronic doxorubicin-induced cardiotoxicity when administered only once per week. Clin Cancer Res. 2000;6(4):1337-41.
van Acker, F. A., van Acker, S. A., Kramer, K., Haenen, G. R., Bast, A., & van der Vijgh, W. J. (2000). 7-monohydroxyethylrutoside protects against chronic doxorubicin-induced cardiotoxicity when administered only once per week. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 6(4), pp. 1337-41.
van Acker FA, et al. 7-monohydroxyethylrutoside Protects Against Chronic Doxorubicin-induced Cardiotoxicity when Administered Only once Per Week. Clin Cancer Res. 2000;6(4):1337-41. PubMed PMID: 10778960.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 7-monohydroxyethylrutoside protects against chronic doxorubicin-induced cardiotoxicity when administered only once per week. AU - van Acker,F A, AU - van Acker,S A, AU - Kramer,K, AU - Haenen,G R, AU - Bast,A, AU - van der Vijgh,W J, PY - 2000/4/25/pubmed PY - 2000/8/6/medline PY - 2000/4/25/entrez SP - 1337 EP - 41 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 6 IS - 4 N2 - Doxorubicin is a very effective antitumor agent, but its clinical use is limited by the occurrence of a cumulative dose-related cardiotoxicity, resulting in congestive heart failure. 7-Monohydroxyethylrutoside (monoHER), a flavonoid belonging to the semisynthetic hydroxyethylrutoside family, has been shown to protect against doxorubicin-induced cardiotoxicity when administered i.p. at a dose of 500 mg/kg five times/week in combination with a weekly i.v. dose of doxorubicin. Such a dosing schedule would be very inconvenient in clinical practice. We therefore investigated a dosing schedule of one administration of monoHER just before doxorubicin. The electrocardiogram was measured telemetrically in mice after the combined treatment of doxorubicin (4 mg/kg, i.v.) with one dose of monoHER (500 mg/kg, i.p., administered 1 h before doxorubicin) for 6 weeks. These data were compared with the five times/week schedule (500 mg/kg, i.p., administered 1 h before doxorubicin and every 24 h for 4 days). The increase of the ST interval was used as a measure for cardiotoxicity. It was shown that 500 mg/kg monoHER administered only 1 h before doxorubicin provided complete protection against the cardiotoxicity. This protection was present for at least 10 weeks after the last treatment. Because of the short half-life of monoHER, these results suggest that the presence of monoHER is only necessary during the highest plasma levels of doxorubicin. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/10778960/7_monohydroxyethylrutoside_protects_against_chronic_doxorubicin_induced_cardiotoxicity_when_administered_only_once_per_week_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10778960 DB - PRIME DP - Unbound Medicine ER -