Monohydroxyethylrutoside as protector against chronic doxorubicin-induced cardiotoxicity.
1. The clinical use of the antitumour agent, doxorubicin, is largely limited by the development of a cumulative dose-related cardiotoxicity. This toxicity is generally believed to be caused by the formation of oxygen free radicals. In earlier studies it was established that flavonoids, naturally occurring antioxidants, can provide some degree of protection. In this study we investigated whether 7-monohydroxyethylrutoside (monoHER), a powerful antioxidative flavonoid with extremely low toxicity, can provide protection to an extent comparable to the clinically successful Cardioxane (ICRF-187). 2. Balb/c mice of 20-25 g were equipped i.p. with a telemeter to measure ECG. They were given 6 i.v. doses of doxorubicin (4 mg kg-1) at weekly intervals. ICRF-187 (50 mg kg-1) or monoHER (500 mg kg-1) were administered i.p. 1 h before doxorubicin administration. In the 2 monoHER groups the treatment continued with either 1 or 4 additional injections per week. A saline and monoHER treated group served as controls. After these 6 weeks, they were observed for another 2 weeks. 3. At the end of this study (week 8) the ST interval had increased by 16.7 +/- 2.7 ms (mean +/- s.e. mean) in doxorubicin-treated mice. At that time, the ST interval had increased by only 1.8 +/- 0.9 ms in ICRF-187 co-mediated mice and in monoHER co-medicated mice by only 1.7 +/- 0.8 and 5.1 +/- 1.7 ms (5- and 2-day schedule, respectively, all P < 0.001 relative to doxorubicin and not significantly different from control). The ECG of the control animals did not change during the entire study. The QRS complex did not change in either group.4. It can be concluded that monoHER protects against doxorubicin-induced cardiotoxicity and merits further evaluation in this respect.
van Acker
S A
SA
LACDR, Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, De Boelelaan, Amsterdam, The Netherlands.
Kramer
K
K
Grimbergen
J A
JA
van den Berg
D J
DJ
van der Vijgh
W J
WJ
Bast
A
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006896:Hydroxyethylrutoside / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D006896:Hydroxyethylrutoside; D004317:Doxorubicin