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Long-term effects of 7-monohydroxyethylrutoside (monoHER) on DOX-induced cardiotoxicity in mice.
Cancer Chemother Pharmacol 2007; 60(4):509-14CC

Abstract

Doxorubicin (DOX) is a potent antitumor agent for different types of cancer, but the cumulative, dose-related cardiotoxicity limits its clinical use. The incidence of abnormal cardiac function after treatment with DOX appears to increase with time. Therefore, late cardiotoxicity is-especially in young surviving patients-a major concern. The aim of this study was to evaluate in mice whether the semisynthetic flavonoid 7-monohydroxyethylrutoside (monoHER) also protected against DOX-induced cardiotoxicity after a long period of follow-up. Four groups of 6 Balb/c mice were treated weekly during 6 weeks with saline, DOX alone (4 mg/kg i.v.), DOX preceded by monoHER (500 mg/kg i.p.), or DOX preceded by monoHER followed by long-term weekly monoHER injections during the observation period of 6 months. Half of the mice treated with DOX only developed DOX-induced heart failure and died within 6 months of observation. Two mice co-treated with monoHER showed weight loss and shortness of breath, whereas one mouse was found dead in its cage known with weight loss. The group receiving DOX plus long-term repeated doses of monoHER started to lose weight. Five out of six mice in this group developed shortness of breath and died before the end of the study with symptoms of cardiac failure induced by DOX. Statistical comparison of the histological heart damage between the different experimental groups was not possible, because the animals died at different time-points in the observation period and DOX-induced cardiotoxicity progressed with time. Nevertheless, it was clear that the initial cardioprotective effect of monoHER was not prolonged during the half-year observation period. It was even suggested that addition of repeated doses of monoHER tended to aggravate DOX-induced cardiotoxicity. It cannot be excluded that the dose and frequency of monoHER administration is crucial in obtaining an optimal antioxidant activity without a pro-oxidant activity of monoHER.

Authors+Show Affiliations

Department of Medical Oncology, VU University Medical Center, 1081 HV, CCA-Building, room 1.38, De Boelelaan 1117, Amsterdam, The Netherlands. ame.bruynzeel@vumc.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17177067

Citation

Bruynzeel, Anna M E., et al. "Long-term Effects of 7-monohydroxyethylrutoside (monoHER) On DOX-induced Cardiotoxicity in Mice." Cancer Chemotherapy and Pharmacology, vol. 60, no. 4, 2007, pp. 509-14.
Bruynzeel AM, Vormer-Bonne S, Bast A, et al. Long-term effects of 7-monohydroxyethylrutoside (monoHER) on DOX-induced cardiotoxicity in mice. Cancer Chemother Pharmacol. 2007;60(4):509-14.
Bruynzeel, A. M., Vormer-Bonne, S., Bast, A., Niessen, H. W., & van der Vijgh, W. J. (2007). Long-term effects of 7-monohydroxyethylrutoside (monoHER) on DOX-induced cardiotoxicity in mice. Cancer Chemotherapy and Pharmacology, 60(4), pp. 509-14.
Bruynzeel AM, et al. Long-term Effects of 7-monohydroxyethylrutoside (monoHER) On DOX-induced Cardiotoxicity in Mice. Cancer Chemother Pharmacol. 2007;60(4):509-14. PubMed PMID: 17177067.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term effects of 7-monohydroxyethylrutoside (monoHER) on DOX-induced cardiotoxicity in mice. AU - Bruynzeel,Anna M E, AU - Vormer-Bonne,Suzanne, AU - Bast,Aalt, AU - Niessen,Hans W M, AU - van der Vijgh,Wim J F, Y1 - 2006/12/20/ PY - 2006/09/26/received PY - 2006/11/28/accepted PY - 2006/12/21/pubmed PY - 2007/9/20/medline PY - 2006/12/21/entrez SP - 509 EP - 14 JF - Cancer chemotherapy and pharmacology JO - Cancer Chemother. Pharmacol. VL - 60 IS - 4 N2 - Doxorubicin (DOX) is a potent antitumor agent for different types of cancer, but the cumulative, dose-related cardiotoxicity limits its clinical use. The incidence of abnormal cardiac function after treatment with DOX appears to increase with time. Therefore, late cardiotoxicity is-especially in young surviving patients-a major concern. The aim of this study was to evaluate in mice whether the semisynthetic flavonoid 7-monohydroxyethylrutoside (monoHER) also protected against DOX-induced cardiotoxicity after a long period of follow-up. Four groups of 6 Balb/c mice were treated weekly during 6 weeks with saline, DOX alone (4 mg/kg i.v.), DOX preceded by monoHER (500 mg/kg i.p.), or DOX preceded by monoHER followed by long-term weekly monoHER injections during the observation period of 6 months. Half of the mice treated with DOX only developed DOX-induced heart failure and died within 6 months of observation. Two mice co-treated with monoHER showed weight loss and shortness of breath, whereas one mouse was found dead in its cage known with weight loss. The group receiving DOX plus long-term repeated doses of monoHER started to lose weight. Five out of six mice in this group developed shortness of breath and died before the end of the study with symptoms of cardiac failure induced by DOX. Statistical comparison of the histological heart damage between the different experimental groups was not possible, because the animals died at different time-points in the observation period and DOX-induced cardiotoxicity progressed with time. Nevertheless, it was clear that the initial cardioprotective effect of monoHER was not prolonged during the half-year observation period. It was even suggested that addition of repeated doses of monoHER tended to aggravate DOX-induced cardiotoxicity. It cannot be excluded that the dose and frequency of monoHER administration is crucial in obtaining an optimal antioxidant activity without a pro-oxidant activity of monoHER. SN - 0344-5704 UR - https://www.unboundmedicine.com/medline/citation/17177067/Long_term_effects_of_7_monohydroxyethylrutoside__monoHER__on_DOX_induced_cardiotoxicity_in_mice_ L2 - https://dx.doi.org/10.1007/s00280-006-0395-2 DB - PRIME DP - Unbound Medicine ER -