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

Aim: The 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. Methods: Thirty 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. Results: In 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. Conclusion: This study may guide clinical trials using ATP and melatonin to prevent methylphenidate-induced myocardial injury. Copyright © 2025 Emir, Bulut, Suleyman, Mammadov, Yucel, Cicek, Yazici, Altuner, Gunay and Suleyman.