Sahin, OrhanAkturk, GozdeMicili, Serap CilakerDoruk, Ozlem GursoyKarapinar, FaziletHocaoglu, NilErgur, Bekir Ugur2024-09-182024-09-1820230022-35732042-7158https://doi.org/10.1093/jpp/rgac089https://hdl.handle.net/20.500.12483/7615Objectives The aim of this study is to evaluate the protective effect of nicorandil, a selective mitochondrial K-ATP channel opener, on QT prolongation and myocardial damage induced by amitriptyline. Methods The dose of amitriptyline (intraperitoneal, i.p.) that prolong the QT interval was found 75 mg/kg. Rats were randomized into five groups the control group, amitriptyline group, nicorandil (selective mitochondrial K-ATP channel opener, 3 mg/kg i.p.) + amitriptyline group, 5-hdyroxydecanoate (5-HD, selective mitochondrial K-ATP channel blocker, 10 mg/kg i.p.) + amitriptyline group and 5-HD + nicorandil + amitriptyline group. Cardiac parameters, biochemical and histomorphological/immunohistochemical examinations were evaluated. p < 0.05 was accepted as statistically significant. Key findings Amitriptyline caused statistically significant prolongation of QRS duration, QT interval and QTc interval (p < 0.05). It also caused changes in tissue oxidant (increase in malondialdehyde)/anti-oxidant (decrease in glutathione peroxidase) parameters (p < 0.05), myocardial damage and apoptosis (p < 0.01 and p < 0.001). While nicorandil administration prevented amitriptyline-induced QRS, QT, QTc prolongation (p < 0.05), myocardial damage and apoptosis (p < 0.05), it did not affect the changes in oxidative parameters (p > 0.05). Conclusions Our results suggest that nicorandil, a selective mitochondrial K-ATP channel opener, plays a protective role in amitriptyline-induced QT prolongation and myocardial damage. Mitochondrial K-ATP channel opening and anti-apoptotic effects may play a role in the cardioprotective effect of nicorandil.eninfo:eu-repo/semantics/closedAccessamitriptylinenicorandilQT prolongationcardiotoxicitymitoK(ATP) channelEffect of the selective mitochondrial KATP channel opener nicorandil on the QT prolongation and myocardial damage induced by amitriptyline in ratsArticle75341542610.1093/jpp/rgac089365272522-s2.0-85150079473Q2WOS:000898595600001Q2