• Klíčová slova
• DIMETHOXYBENFLURON,
• MeSH
• antitumorózní látky škodlivé účinky   MeSH
• daunomycin škodlivé účinky   MeSH
• finanční podpora výzkumu jako téma MeSH
• kardiomyopatie chemicky indukované   MeSH
• krysa rodu rattus MeSH
• troponin diagnostické užití   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

• Klíčová slova
• BENFLURON,
• MeSH
• antitumorózní látky aplikace a dávkování   škodlivé účinky   MeSH
• biochemie MeSH
• hematologie MeSH
• králíci MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH

• MeSH
• alkoholdehydrogenasa metabolismus   MeSH
• antitumorózní látky chemie   metabolismus   MeSH
• fluoreny chemie   metabolismus   MeSH
• hepatocyty enzymologie   metabolismus   MeSH
• hydroxysteroidní dehydrogenasy metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• oxidace-redukce MeSH
• Check Tag
• lidé MeSH

• MeSH
• antitumorózní látky normy   MeSH
• bezpečnost MeSH
• daunomycin MeSH
• fixní kombinace léků normy   MeSH
• králíci MeSH
• srdce účinky léků   MeSH
• troponin T analýza   biosyntéza   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH

Anthracycline derivatives belong among the most effective antineoplastic drugs but their therapeutic use is limited by their side effects--a dose-related cardiotoxicity. The influence of repeated i.v. administration (once weekly, max. 10 weeks) of new antineoplastic agents--dimethoxybenfluron (DMB) (3,9-dimethoxybenfluron hydrochloride, C23H24O4NCl, M.w. 413.9, Institute of Experimental Biopharmaceutics, Czech Academy of Sciences, Hradec Králové, Czech Republic; 12 or 24 mg base/kg) and Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5,11-dioxo-5,6-dihydro-11H- indeno[1,2c]isoquinoline hydrochloride), C20H19N2O3Cl, M.w. 370.84, Research Institute for Pharmacy and Biochemistry, Prague, Czech Republic; 5 or 10 mg/kg) on cardiovascular, biochemical, haematological and histological parameters were studied in rabbits in vivo. Data obtained in these groups were compared with the group with experimentally induced cardiomyopathy (daunorubicin 50 mg/m2 i.v.) and with the control group (saline 1 ml/kg). Only mild and mostly no significant changes of the cardiovascular parameters (DMB 12 group: PEP:LVET ratio--0.408-0.502, LV dP/dtmax.--1337.0 kPa/s; DMB 24 group: PEP:LVET ratio--0.407-0.433, LV dP/dtmax.--1438.2 kPa/s), biochemical parameters (decrease in natrium, ALP and increase in glucose, GPX and GSH levels) and haematological parameters (increase in erythrocytes and decrease in leukocytes after the larger dose of the drug) were found in the dimethoxybenfluron groups. Repeated administration of the lower dose of Oracin induced only mild and mostly no significant changes of parameters (PEP:LVET ratio--0.393-0.475, LV dP/dtmax.--1092.4 kPa/s) in comparison with the control group. Though significant in some intervals, only a mild oscillation of the PEP:LVET ratio (0.368-0.446), decrease in LV dP/dtmax. (991.2 kPa/s) and--in comparison with control group--significantly higher blood pressure and lower heart rate were found after the higher dose of Oracin. In the most of haematological and biochemical parameters (with the exception of chlorides, protein and albumin levels) no significant changes were present. Histological examination of the heart revealed normal structure of the myocardium including minute changes of myocardium following administration of antineoplastic agents in all groups. Administration of new antineoplastic agents induced mostly mild changes of the followed-up parameters (PEP:LVET ratio, LV dP/dtmax., heart rate, levels of cardiac troponin T, survival of animals, haematological and biochemical parameters); the values of parameters were mostly significantly different from those in rabbits with daunorubicin-induced cardiomyopathy. On the basis of our results it is possible to conclude that the administration of dimethoxybenflurone and Oracin did not induce signs of cardiotoxicity in rabbits in vivo. This observation is considered to be important from the viewpoint of possible further clinical use of these new antineoplastic agents.

• MeSH
• antitumorózní látky toxicita   MeSH
• daunomycin toxicita   MeSH
• ethanolaminy toxicita   MeSH
• fluoreny toxicita   MeSH
• funkce levé komory srdeční účinky léků   MeSH
• hemodynamika účinky léků   MeSH
• isochinoliny toxicita   MeSH
• králíci MeSH
• krevní tlak účinky léků   MeSH
• myokard metabolismus   patologie   MeSH
• srdce účinky léků   MeSH
• srdeční frekvence účinky léků   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH

Recently, cardiac troponin T (cTnT) has been shown to be a sensitive marker of anthracycline-induced cardiomyopathy. In our study, the cardiotoxicity of repeated i.v. administration (once a week, 10 administrations) of daunorubicin combined with new antineoplastic drugs (with mild side-effects) were followed in two groups of rabbits: 1) Dimefluron (3,9-dimethoxybenfluron hydrochloride-12 mg/kg) + daunorubicin (3 mg/kg), 2) Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5,11-dioxo-5,6-dihydro-11H- indeno[1,2c]isoquinoline hydrochloride--10 mg/kg) + daunorubicin (3 mg/kg) and compared with the control group (saline--1 ml/kg) and the group with experimentally induced cardiomyopathy (daunorubicin--3 mg/kg). The concentration of cTnT in heparinized plasma samples was measured using commercial kit (Roche). In the control group, plasma levels of cTnT were always within the physiological range (i.e. lower than 0.1 microgram/l) during the experiment. During the development of daunorubicin-induced cardiomyopathy, after the eighth administration of drug, cTnT was significantly higher (0.31 +/- 0.11 microgram/l) in animals with premature deaths compared with the rest of the group (0.04 +/- 0.03 microgram/l). The animals with pathological values of cTnT were at higher risk of premature deaths (P = 0.0006). The combination of daunorubicin either with Oracin or with Dimefluron caused neither significant changes of cTnT levels nor significant deterioration of other followed-up parameters (especially, functional and toxicological parameters). Similarly to the daunorubicin group, the animals with pathological levels of cTnT after the eighth administration of antineoplastic drugs were at higher risk of premature death (P = 0.025). Our results show that the plasma concentration of cardiac troponin T could be a suitable predictive marker of cardiotoxicity of antineoplastic drugs.

• MeSH
• antibiotika antitumorózní aplikace a dávkování   toxicita   MeSH
• biologické markery krev   MeSH
• daunomycin aplikace a dávkování   toxicita   MeSH
• ethanolaminy aplikace a dávkování   toxicita   MeSH
• fluoreny aplikace a dávkování   toxicita   MeSH
• isochinoliny aplikace a dávkování   toxicita   MeSH
• kardiomyopatie chemicky indukované   diagnóza   MeSH
• králíci MeSH
• protokoly antitumorózní kombinované chemoterapie toxicita   MeSH
• troponin T krev   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH