Emir Izzet, Bulut Seval, Suleyman Bahadır, Mammadov Renad, Yucel Nurinisa, Cicek Betul, Yazici Gulce Naz, Altuner Durdu, Gunay Murat, Suleyman Halis
Department of Cardiovascular Surgery, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan, Türkiye.
Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Türkiye.
Front Pharmacol. 2025 Jan 3;15:1503032. doi: 10.3389/fphar.2024.1503032. eCollection 2024.
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.
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.
In MP group, MDA, adrenaline, noradrenaline, dopamine, TP I, and CK-MB levels increased ( < 0.001) and tGSH, SOD, and CAT levels decreased ( < 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 ( < 0.001). Catecholamine levels were measured lower in the MSMP group compared to the MP group ( < 0.001). TP I and CK-MB levels were lower in ATMP, MSMP and MLMP groups compared to MP ( < 0.05), with the lowest being in rats given ATP ( < 0.001). ATP, melatonin, and metirozin applications were effective to different degrees in preventing histopathological changes.
This study may guide clinical trials using ATP and melatonin to prevent methylphenidate-induced myocardial injury.
本研究旨在采用生化和组织病理学方法，探讨三磷酸腺苷（ATP）、甲酪氨酸和褪黑素对大鼠可能存在的哌甲酯心脏毒性的保护作用。
将30只大鼠分为五组：健康组（HG）、哌甲酯组（MP）、ATP+哌甲酯组（ATMP）、甲酪氨酸+哌甲酯组（MSMP）和褪黑素+哌甲酯组（MLMP）。ATP（5mg/kg）每日腹腔注射1次，甲酪氨酸（50mg/kg）每日口服2次，褪黑素（10mg/kg）每日口服1次。在给予ATP、甲酪氨酸和褪黑素1小时后，哌甲酯（10mg/kg）每日口服给药1次。该方案重复30天。随后，从动物尾静脉采集血样，以测量肾上腺素、去甲肾上腺素、多巴胺、肌钙蛋白I（TP I）和肌酸激酶MB（CK-MB）水平；然后对动物实施安乐死并提取心脏组织。对组织进行丙二醛（MDA）、总谷胱甘肽（tGSH）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）分析以及组织病理学分析。
与HG组相比，MP组的MDA、肾上腺素、去甲肾上腺素、多巴胺、TP I和CK-MB水平升高（<0.001），tGSH、SOD和CAT水平降低（<0.001），并出现组织病理学损伤。与MP组相比，ATMP、MSMP和MLMP组的氧化水平较低，抗氧化水平较高（<0.001）。与MP组相比，MSMP组的儿茶酚胺水平较低（<0.001）。与MP组相比，ATMP、MSMP和MLMP组的TP I和CK-MB水平较低（<0.05），其中给予ATP的大鼠最低（<0.001）。ATP、褪黑素和甲酪氨酸的应用在预防组织病理学变化方面有不同程度的效果。
本研究可为使用ATP和褪黑素预防哌甲酯引起的心肌损伤的临床试验提供指导。
