title: Correlation between serum levels of cardiac troponin-T and the severity of the chronic cardiomyopathy induced by doxorubicin.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Applied Pharmacology Research (HFD-910), Center for Drug Evaluation and Research, Food and Drug Administration, Laurel, MD 20708, USA. hermaneu@cder.fda.gov
authors.forename: E H
authors.initials: EH
authors.lastname: Herman
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: S E
authors.initials: SE
authors.lastname: Lipshultz
authors.forename: N
authors.initials: N
authors.lastname: Rifai
authors.forename: D
authors.initials: D
authors.lastname: Chadwick
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: Z X
authors.initials: ZX
authors.lastname: Yu
authors.forename: V J
authors.initials: VJ
authors.lastname: Ferrans
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D015415:Biomarkers; D009202:Cardiomyopathies / Q000097:blood* / Q000139:chemically induced* / Q000473:pathology; D002908:Chronic Disease; D004317:Doxorubicin / Q000633:toxicity*; D016903:Drug Monitoring / Q000379:methods*; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D020107:Troponin T / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D020107:Troponin T; D004317:Doxorubicin