Cardioprotective properties of O-(β-hydroxyethyl)-rutosides in doxorubicin-pretreated BALB/c mice

• Published in: Cancer research (Chicago, Ill.) Vol. 53; no. 19; pp. 4603 - 4607
• Main Authors: VAN ACKER, S. A. B. E, VOEST, E. E, BEEMS, D. B, MADHUIZEN, H. T, DE JONG, J, BAST, A, VAN DER VIJGH, W. J. F
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-10-1993
• Subjects: Animals; Biological and medical sciences; Body Weight - drug effects; Colforsin - pharmacology; Doxorubicin - administration & dosage; Doxorubicin - toxicity; Drug Administration Schedule; Drug toxicity and drugs side effects treatment; Free Radical Scavengers; Heart - drug effects; Heart Rate - drug effects; Hydroxyethylrutoside - administration & dosage; Hydroxyethylrutoside - analogs & derivatives; Hydroxyethylrutoside - pharmacology; Injections, Intraperitoneal; Injections, Intravenous; Isoproterenol - pharmacology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Myocardial Contraction - drug effects; Myocardium - pathology; Pharmacology. Drug treatments; Razoxane - pharmacology; Time Factors; Toxicity: cardiovascular system; Antineoplastic agent; Heart; Intraperitoneal administration; Toxicity; Rodentia; Rutoside; Cardiovascular disease; Flavonoid; Prevention; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Animal; Anthracyclins
• ISSN: 0008-5472; 1538-7445

Chronic doxorubicin-induced cardiotoxicity is believed to be caused by the formation of oxygen free radicals. Thus O-(beta-hydroxyethyl)-rutosides, a standardized flavonoid mixture (Venoruton) with iron chelating and radical scavenging activity, might provide protection. Therefore, we investigated the (cardio)protective effect of Venoruton (1.5 g/kg injected i.p. on days 1-5, 8-12, 15-19, and 22-26) in BALB/c mice treated with doxorubicin (4 mg/kg injected i.v. on days 1, 8, 15, and 22) compared with mice treated with doxorubicin alone. Saline-treated animals served as controls. No mortality was encountered in either of the groups; weight gain data suggest little general toxicity of this dose schedule. The basal frequency of the isolated right atria was increased in doxorubicin-pretreated animals as compared to control animals (468 +/- 22 and 366 +/- 20 beats/min, respectively). Venoruton coadministration diminished this increase (373 +/- 17 beats/min). The -log of the concentration giving 50% effect of l-isoprenaline on the right atrium was changed after doxorubicin pretreatment (8.33 +/- 0.04 versus 8.86 +/- 0.06 for control animals). Venoruton coadministration resulted in a smaller shift in the -log of the concentration giving 50% effect (8.51 +/- 0.10) than with doxorubicin alone. The extent of cardiotoxicity found in the functional studies was confirmed by histological scoring of heart ventricle damage. It can be concluded that Venoruton has the potential to protect against doxorubicin-induced cardiotoxicity.