Cardiac troponin T as a marker of myocardial damage caused by antineoplastic drugs in rabbits

Abstract

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.

In vitro and in vivo examination of cardiac troponins as biochemical markers of drug-induced cardiotoxicity

“…The use of cTnT as a biomarker of doxorubicin cardiotoxicity in animal studies was first reported by Seino et al, in spontaneously hypertensive rats (Seino et al, 1993). Numerous subsequent studies have then confirmed the utility of serum cTnT monitoring to detect the extent of anthracyclineinduced cardiac damage (Herman et al, 1998(Herman et al, ,1999Adamcova et al, 1999;Simunek et al, 2003).…”

Experimental determination of diagnostic window of cardiac troponins in the development of chronic anthracycline cardiotoxicity and estimation of its predictive value

“…In the first cycle, we sought to determine whether a single clinically relevant dose of ANT can induce a significant cTn release and whether this may identify animals with a higher future cardiotoxicity risk. We performed the same analysis after five ANT cycles (~250 mg/m 2 ), when we previously found the first significant cTn elevation while cardiac function was still normal [10,15]. Eight cycles were then used as the interval in which the first significant drop of LV systolic function appears in this model.…”

“…Scattered data in the literature, including our own [15][16][17], has suggested that ANT-induced cardiac damage is associated with a relatively prolonged release of cTns, but further details are lacking. A significant increase of cTns after ANT exposure has also been found in numerous clinical studies (reviewed in [18]).…”

Plasma Cardiac Necrosis Markers C-Troponin I and Creatine Kinase, Associated with Increased Malondialdehyde Levels, Induced in Rabbits by Means of 5-Aminolevulinic Acid Injection

“…As shown in figure 1 , the administration of 5-ALA is associated with the appearance of both c-Tn I and CK. We and other authors have previously detected these markers in rabbit plasma [31,32] , which can be done using antibodies against human c-Tn I because the peptide sequences in human and rabbit cardiac troponins are highly similar or identical [33][34][35] and allow the cross-reactivity reactions observed in various species [36,37] .…”