کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2597759 | 1562419 | 2007 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: In vitro and in vivo examination of cardiac troponins as biochemical markers of drug-induced cardiotoxicity In vitro and in vivo examination of cardiac troponins as biochemical markers of drug-induced cardiotoxicity](/preview/png/2597759.png)
Cardiac troponin T (cTnT) and troponin I (cTnI) are becoming acknowledged as useful biochemical markers of drug-induced cardiotoxicity. In this study we examined the release kinetics of cTnT and cTnI using an in vitro model of isolated rat neonatal ventricular cardiomyocytes (NVCM, 72 h treatment with 0.1–3 μM of daunorubicin) and compared it with data from a rabbit model of chronic anthracycline-induced cardiomyopathy in vivo (3 mg/kg of daunorubicin weekly, 10 weeks). In cell-culture media, the cTnI and cTnT concentrations were concentration- and time-dependently increasing in response to daunorubicin exposure and were negatively exponentially related to cardiomyocyte viability. With 3 μM daunorubicin, the relative increase of AUC of cTnT and cTnI was 2.4- and 5.3-fold higher than the increase of LDH activity, respectively. In rabbits, the daunorubicin-induced cardiomyopathy was associated with progressive increase of both cTnT and cTnI. Although the correlation between cTnT and cTnI cumulative release (AUCs) was found (R = 0.81; P < 0.01) and both cardiac troponins corresponded well with the echocardiographically-assessed systolic dysfunction (R = 0.83 and 0.81 for cTnT and cTnI, respectively; P < 0.001), the first significant increase in cTnI levels was observed earlier (at a cumulative daunorubicin dose of 200 mg/m2) than with cTnT (350 mg/m2). In conclusion, our study has confirmed cTnT and cTnI as very sensitive and specific markers of anthracycline-induced cardiotoxicity. The troponins can become not only the bridge between the clinical and experimental studies of drug-induced cardiotoxicity but also the linkage between the preclinical experiments in vitro and in vivo.
Journal: Toxicology - Volume 237, Issues 1–3, 31 July 2007, Pages 218–228