Evaluation
of Cardiac Effects of the New Antineoplastic Drug
- Dimethoxybenfluron - in the Rabbit
J.
MACHÁČKOVÁ1, M. ADAMCOVÁ2,
Y. MAZUROVÁ3, R. HRDINA4,
M. NOBILIS5
1Department
of Pharmacology, 2Department
of Physiology, and 3Department
of Histology and Embryology, Charles University
in Prague, Faculty of Medicine in Hradec
Králové, 4Department
of Pharmacology and Toxicology, Charles
University in Prague, Faculty of Pharmacy in
Hradec Králové, 5Institute
of Experimental Biopharmaceutics, Czech Academy
of Sciences, Hradec Králové, Czech Republic
Received September 1,
2000
Accepted February 20, 2001
Summary
Cardiotoxicity
ranks among the most serious adverse effects of
some cytostatics. The cardiac effects of repeated
i.v. administration of a new antineoplastic
agent, dimethoxybenfluron (once a week, 10
administrations), were investigated in rabbits
with respect to cardiac function and the release
of cardiac troponin T (cTnT). Different doses of
dimethoxybenfluron were administered to two
groups of animals (12 mg/kg; n = 7 and 24 mg/kg;
n = 6) and compared with either a control group
(saline 1 ml/kg; n = 6) or a group with
experimentally induced cardiomyopathy
(daunorubicin 50 mg/m2; n = 13). In
daunorubicin-induced cardiomyopathy, cTnT levels
in animals with premature deaths were
significantly higher (0.31±0.11 mg/l) in
comparison with the surviving animals (0.04±0.03
mg/l). However, cardiac TnT levels after the
administration of dimethoxybenfluron in both
doses were within the physiological range (lower
than 0.1 mg/l) during the whole experiment as it
was in the control group. The lack of
cardiotoxicity of this new antineoplastic drug
was supported by the absence of alterations in
PEP:LVET ratio, left ventricle dP/dtmax or
histological heart examination as well as by the
fact that no premature death of animals occurred
following repeated administration of
dimethoxybenfluron. It is possible to conclude
that no signs of cardiotoxicity were observed
following repeated i.v. administration of
dimethoxybenfluron.
Key
words
Cardiac
troponin T · Daunorubicin · Dimethoxybenfluron
· Cardiomyopathy · Antineoplastic drugs
Reprint
requests
Macháčková
Jarmila, M.Sc., Department of Pharmacology,
Faculty of Medicine, Charles University, Šimkova
870, 500 01 Hradec Králové, Czech Republic,
fax: 00420-49-5513597, e-mail: machackovaj@lfhk.cuni.cz
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