Cardiac Troponin T and NT-proBNP as Biomarkers of Early Myocardial Damage in Amitriptyline-Induced Cardiovascular Toxicity in Rats

• Published in: International journal of toxicology 2013-09, Vol.32 (5), p.351-357
• Main Authors: Sorodoc, Victorita, Sorodoc, Laurentiu, Ungureanu, Didona, Sava, Anca, Jaba, Irina M.
• Format: Article
• Language: English
• Subjects: Amitriptyline - adverse effects; Animals; Antidepressive Agents, Tricyclic - adverse effects; Biomarkers - blood; Heart - physiopathology; Heart Diseases - blood; Heart Diseases - chemically induced; Heart Diseases - physiopathology; Long QT Syndrome - blood; Long QT Syndrome - chemically induced; Long QT Syndrome - physiopathology; Male; Myocardium - metabolism; Myocardium - pathology; Natriuretic Peptide, Brain - blood; Peptide Fragments - blood; Rats; Rats, Wistar; Troponin T - blood
• ISSN: 1091-5818; 1092-874X
• DOI: 10.1177/1091581813503888

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.