AUTHOR=Emir Izzet , Bulut Seval , Suleyman Bahadır , Mammadov Renad , Yucel Nurinisa , Cicek Betul , Yazici Gulce Naz , Altuner Durdu , Gunay Murat , Suleyman Halis 

TITLE=Pathogenesis-directed therapy of methylphenidate-induced oxidative heart damage in rats

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 15 - 2024

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1503032

DOI=10.3389/fphar.2024.1503032

ISSN=1663-9812

ABSTRACT=AimThe current study aimed to investigate the protective effects of adenosine triphosphate (ATP), metyrosine, and melatonin on possible methylphenidate cardiotoxicity in rats using biochemical and histopathological methods.MethodsThirty rats were separated into five groups: healthy (HG), methylphenidate (MP), ATP + methylphenidate (ATMP), metyrosine + methylphenidate (MSMP), and melatonin + methylphenidate (MLMP). ATP (5 mg/kg) was given intraperitoneally once daily, metyrosine (50 mg/kg) orally twice daily, and melatonin (10 mg/kg) orally once daily. Methylphenidate (10 mg/kg) was administered orally once daily for 1 h after ATP, metyrosine and melatonin. The protocol was repeated for 30 days. Subsequently, blood samples were taken from the tail veins of the animals to measure adrenaline, noradrenaline, dopamine, troponin I (TP I) and creatine kinase MB (CK-MB) levels; the animals were then euthanized and the heart tissues were extracted. Tissues were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) and histopathologically.ResultsIn MP group, MDA, adrenaline, noradrenaline, dopamine, TP I, and CK-MB levels increased (p < 0.001) and tGSH, SOD, and CAT levels decreased (p < 0.001) compared to HG, and histopathologic damage developed. Oxidant levels were lower and antioxidant levels were higher in ATMP, MSMP, and MLMP groups compared to MP group (p < 0.001). Catecholamine levels were measured lower in the MSMP group compared to the MP group (p < 0.001). TP I and CK-MB levels were lower in ATMP, MSMP and MLMP groups compared to MP (p < 0.05), with the lowest being in rats given ATP (p < 0.001). ATP, melatonin, and metirozin applications were effective to different degrees in preventing histopathological changes.ConclusionThis study may guide clinical trials using ATP and melatonin to prevent methylphenidate-induced myocardial injury.