In spontaneously hypertensive rats, average serum cTnT levels and cardiomyopathy scores correlated with the cumulative dose of doxorubicin, indicating cTnT is a sensitive biomarker for early cardiotoxicity.
Do serum levels of cardiac troponin-T correlate with the severity of doxorubicin-induced cardiomyopathy in spontaneously hypertensive rats?
Serum cTnT levels correlate with cumulative doxorubicin dose and histologic severity of cardiomyopathy in a rat model, suggesting its utility as an early biomarker for cardiotoxicity.
PURPOSE: To investigate, over a wide range of cumulative doxorubicin doses, the feasibility of using serum concentrations of cardiac troponin-T (cTnT) as a biomarker for doxorubicin-induced myocardial damage. MATERIALS AND METHODS: Groups of spontaneously hypertensive rats (SHR) were given 1 mg/kg doxorubicin weekly for 2 to 12 weeks. Cardiomyopathy scores were assessed according to the method of Billingham and serum levels of cTnT were quantified by a noncompetitive immunoassay. Myocardial localization of cTnT was studied by immunohistochemical staining and confocal microscopy. RESULTS: Increases in serum levels of cTnT (0.03 to 0.05 ng/mL) and myocardial lesions (cardiomyopathy scores of 1 or 1.5) were found in one out of five and two out of five SHR given 2 and 4 mg/kg doxorubicin, respectively. All animals given 6 mg/kg or more of doxorubicin had increases in serum cTnT and myocardial lesions. The average cTnT levels and the cardiomyopathy scores correlated with the cumulative dose of doxorubicin (0.13 v 0.4 ng/mL cTnT and scores of 1.4 v 3.0 in SHR given 6 and 12 mg/kg doxorubicin, respectively). Decreased staining for cTnT was observed in cardiac tissue from SHR receiving cumulative doses that caused only minimal histologic alterations (scores of 1 to 1.5). Staining for cTnT decreased simultaneously with increases in the severity of the cardiomyopathy scores. CONCLUSION: cTnT is released from doxorubicin-damaged myocytes. Measurements of serum levels of this protein seem to provide a sensitive means for assessing the early cardiotoxicity of doxorubicin.
Herman et al. (Thu,) conducted a other in Doxorubicin-induced cardiomyopathy. Doxorubicin was evaluated on Correlation between serum levels of cTnT and cardiomyopathy scores. In spontaneously hypertensive rats, average serum cTnT levels and cardiomyopathy scores correlated with the cumulative dose of doxorubicin, indicating cTnT is a sensitive biomarker for early cardiotoxicity.