Cardiac troponin T and NT-proBNP as biomarkers of early myocardial damage in amitriptyline-induced cardiovascular toxicity in rats.
The main objective of this study was to investigate whether cardiac troponin (cTn) and N-terminal, protein B-type natriuretic peptide (NT-proBNP) can be useful as indicators for amitriptyline cardiotoxicity which is a known drug having sublethal toxic cardiac effects. At the same time, this study looked at detecting potential histopathological changes specific to irreversible cardiac injuries in a rat model of amitriptyline cardiotoxicity. Male Wistar rats were randomly divided into 2 groups, control (saline) group and amitriptyline group (100 mg/kg body weight intraperitoneally, equivalent for lethal dose at 50%). Blood was collected 30 minutes after the administration. The cTn was measured using 3 different methods (2 methods designed for human use and a sandwich enzyme immunoassay specific for rat cTnT). The brain natriuretic peptide was measured by 2 different methods (1 for human and 1 specific for rats). Electrocardiography showed that the QRS complex (P < .0001) and the QT interval (P = .002) were significantly prolonged for amitriptyline-treated animals. Troponin T and NT-proBNP had significantly increased levels in all the rats but showed positive results only when using rat-specific quantitative measurement. In certain rats, the histopathological examination identified a few small foci of acute myocardial necrosis. In conclusion, elevation of cTnT and NT-proBNP are early indicators of cardiotoxicity, yet the significance of irreversible myocardial damage in amitriptyline cardiotoxicity needs to be further understood.
Department of Internal Medicine, School of Medicine, Gr. T. Popa University of Medicine and Pharmacy, Spitalul Clinic de Urgente, Sf Spiridon, Iasi, Str Independentei No. 1, Iasi, Romania. Email: laurentiu.sorodoc@gmail.com.
Victorita
V
Sorodoc
Laurentiu
L
Sorodoc
Didona
D
Ungureanu
Anca
A
Sava
Irina M
IM
Jaba
D000639:Amitriptyline / Q000009:adverse effects*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D006321:Heart / Q000503:physiopathology; D006331:Heart Diseases / Q000097:blood* / Q000139:chemically induced / Q000503:physiopathology; D008133:Long QT Syndrome / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D020107:Troponin T / Q000097:blood*
D000929:Antidepressive Agents, Tricyclic; D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000639:Amitriptyline
amitriptyline; brain natriuretic peptide; cardiac troponin; cardiotoxicity; rat