The Effects of Lipid Emulsion, Magnesium Sulphate and Metoprolol in Amitriptyline-Induced Cardiovascular Toxicity in Rats

• Published in: Cardiovascular toxicology 2018-12, Vol.18 (6), p.547-556
• Main Authors: Bora, Saylav, Erdoğan, Mümin Alper, Yiğittürk, Gürkan, Erbaş, Oytun, Parlak, İsmet
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Amitriptyline; Amitriptyline - toxicity; Animals; Anti-Arrhythmia Agents - pharmacology; Antidepressive Agents, Tricyclic - toxicity; Biochemical analysis; Biochemistry; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Calcium-binding protein; Cardiology; Cardiotoxicity; Caspase; Caspase 3 - metabolism; Caspase-3; Electrocardiogram; Electrocardiography; Euthanasia; Fat Emulsions, Intravenous - pharmacology; Heart - drug effects; Heart - physiopathology; Heart diseases; Heart Rate - drug effects; Intoxication; Lipids; Long QT Syndrome - blood; Long QT Syndrome - chemically induced; Long QT Syndrome - physiopathology; Long QT Syndrome - prevention & control; Magnesium sulfate; Magnesium Sulfate - pharmacology; Male; Medical research; Medicine, Experimental; Metoprolol; Metoprolol - pharmacology; Myocardium - metabolism; Myocardium - pathology; Natriuretic Peptide, Brain - blood; Peptide Fragments - blood; Pharmacology/Toxicology; Rats; Rats, Sprague-Dawley; Toxicity; Troponin; Troponin T - blood; Urea
• ISSN: 1530-7905; 1559-0259
• DOI: 10.1007/s12012-018-9466-y

The aim of this study was to evaluate the effects of metoprolol, lipid emulsion and MgSO 4 which can be recommended for prevention of long QT that is one of the lethal consequences of amitriptyline intoxication. Thirty Sprague–Dawley male rats were included. Five groups respectively received the following: saline intraperitoneally (i.p.); amitriptyline (AMT) 100 mg/kg per os (p.o.) and saline i.p.; AMT 100 mg/kg p.o. and 5 mg/kg metoprolol i.p.; AMT 100 mg/kg p.o. and 20 ml/kg lipid emulsion i.p.; AMT 100 mg/kg p.o. and 75 mg/kg MgSO 4 i.p. After 1 h, all groups were analysed by ECG recordings in DII lead; their blood was taken for biochemical examination and euthanasia was performed. For histological examination, cardiac tissues were removed and sections were prepared. QTc was significantly reduced in treatment groups compared to the AMT+saline group. When compared with the AMT+saline, lipid emulsion did not affect pro-BNP and troponin levels in biochemical analysis, but it significantly reduced Caspase 3 expression in histological examination. In the group treated with AMT and metoprolol, there was no significant effect on Caspase 3 expression. In MgSO 4 -treated group, there was a significant decrease in troponin, pro-BNP and urea levels biochemically and significant decrease in Caspase 3 expression histologically when compared with the control group. With further studies including clinical studies, MgSO 4 , lipid emulsion or metoprolol may be used to improve AMT-induced cardiotoxicity. They can possibly become alternative approaches in the future for suicidal or accidental intoxication of tricyclic antidepressant in emergency departments.