Adamcová M, Gersl V, Hrdina R, Melka M, Mazurová Y, Vávrová J, Palicka V, Kokstein Z
Department of Physiology, Charles University Faculty of Medicine in Hradec Králové, Czech Republic.
J Cancer Res Clin Oncol. 1999;125(5):268-74. doi: 10.1007/s004320050273.
Anthracycline derivatives are among the most effective antineoplastic drugs but their therapeutic use is limited by their adverse effects. The cardiac side-effects of antineoplastic drugs were investigated in rabbits in vivo from the viewpoint of release of cardiac troponin T (cTnT) measured by Elecsys Troponin T STAT immunoassay (Boehringer Mannheim, Germany). No increase in cTnT was found following administration of a single dose of daunorubicin (3 mg/kg i.v., n = 4). During development of daunorubicin-induced cardiomyopathy (daunorubicin 3 mg/kg i.v., once a week; maximum nine administrations, n = 7), the levels of cTnT were within the physiological range (i.e. cTnT <0.1 microg/l) at the beginning of the experiment and before and after the 5th administration, but the pathological values of cTnT after the 8th administration in 43% animals (0.22+/-0.08 microg/l) correlated with their premature death. In the control group, the levels of cTnT were always lower than 0.1 microg/l during the experiment. Following administration of a new antineoplastic drug - Oracin [6-[2-(2-hydroxyethyl) aminoethyl]-5,11-dioxo-5,6-dihydro-11H-indeno [1,2-c]-isoquinoline hydrochloride, 10 mg/kg i.v., once weekly, ten administrations, n = 7], there was no increase in cTnT levels. These findings correlated with the PEP: LVET index, histological examination and no animal succumbing to premature death. It is possible to conclude that cTnT is a useful marker for the prediction of experimentally induced anthracycline cardiomyopathy and for the evaluation of cardiotoxic (and, possibly, cardioprotective) effects of new drugs in rabbits.
蒽环类衍生物是最有效的抗肿瘤药物之一,但其治疗用途因不良反应而受到限制。从通过Elecsys肌钙蛋白T STAT免疫测定法(德国宝灵曼公司)测量的心肌肌钙蛋白T(cTnT)释放角度,在兔体内研究了抗肿瘤药物的心脏副作用。静脉注射单剂量柔红霉素(3mg/kg,n = 4)后未发现cTnT升高。在柔红霉素诱导的心肌病发展过程中(静脉注射柔红霉素3mg/kg,每周一次;最多给药九次,n = 7),实验开始时以及第5次给药前后,cTnT水平在生理范围内(即cTnT<0.1μg/l),但在43%的动物中,第8次给药后的cTnT病理值(0.22±0.08μg/l)与它们的过早死亡相关。在对照组中,实验期间cTnT水平始终低于0.1μg/l。静脉注射一种新的抗肿瘤药物——奥拉辛[6-[2-(2-羟乙基)氨基乙基]-5,11-二氧代-5,6-二氢-11H-茚并[1,2-c]-异喹啉盐酸盐,10mg/kg,每周一次,给药十次,n = 7]后,cTnT水平没有升高。这些发现与PEP:LVET指数、组织学检查以及无动物过早死亡相关。可以得出结论,cTnT是预测实验性诱导的蒽环类心肌病以及评估兔体内新药心脏毒性(可能还有心脏保护作用)的有用标志物。