Yuan Xiaohong, Wen Bokai, Hu Xin, Yang Mingyu, Han Liqun, Zhao Shengjie, Zhang Jianhai, Ma Yanqin
College of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi, 030801, China.
College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, China.
Poult Sci. 2025 May 21;104(8):105325. doi: 10.1016/j.psj.2025.105325.
Co-exposure to geogenic arsenic and fluoride is widely recognized in numerous countries and has been shown to induce severe cardiac injury in both humans and animals. Our previous studies have demonstrated that mitochondria are primary targets of arsenic and fluoride toxicity, as evidenced by alterations in ultrastructure, mitochondrial membrane potential, respiratory chain function, etc. Therefore, targeting mitochondrial homeostasis to develop pharmacological interventions for mitigating arsenic and fluoride-induced cardiotoxicity holds significant promise. Melatonin has emerged as a potent antioxidant and free radical scavenger. In this study, we reveal the substantial therapeutic potential of melatonin in mitigating arsenic and fluoride-induced cardiac injury in chicken models. A total of 72 one-day-old male Hy-Line Brown broilers were randomly allocated into eight groups: Control Group (basal diet), Arsenic Group (36 mg/kg AsO in diet), Fluoride Group (400 mg/kg NaF in diet), Arsenic + Fluoride Group (36 mg/kg AsO and 400 mg/kg NaF in diet), Melatonin Group (2.5 mg/kg melatonin in diet), Arsenic + Melatonin Group (36 mg/kg AsO and 2.5 mg/kg melatonin in diet), Fluoride + Melatonin Group (400 mg/kg NaF and 2.5 mg/kg melatonin in diet), and Arsenic + Fluoride + Melatonin Group (36 mg/kg AsO, 400 mg/kg NaF, and 2.5 mg/kg melatonin in diet). Following a 23-week intervention with arsenic, fluoride, or their combination, the chickens exhibited significant cardiac damage and myocardial fibrosis. This was evidenced by elevated serum levels of lactate dehydrogenase (LDH), aspartic transaminase (AST), and troponin I (cTn-I), as well as marked changes observed in histopathological examinations. Dietary supplementation with melatonin significantly mitigated these cardiac damages induced by arsenic and fluoride. Mechanistically, we identified that melatonin exerted cardioprotective effects by reducing oxidative stress and apoptosis, and by restoring mitochondrial homeostasis through attenuating pathological mitochondrial fission, enhancing mitochondrial fusion, and promoting mitochondrial biogenesis. Collectively, our findings highlight melatonin as a potent cardioprotective agent against arsenic and fluoride-induced heart injury in chickens.
在许多国家，同时接触地质源砷和氟化物的情况广泛存在，并且已证明这会在人类和动物中引发严重的心脏损伤。我们之前的研究表明，线粒体是砷和氟化物毒性的主要靶点，超微结构、线粒体膜电位、呼吸链功能等方面的改变都证明了这一点。因此，针对线粒体稳态开发减轻砷和氟化物诱导的心脏毒性的药物干预措施具有重大前景。褪黑素已成为一种强大的抗氧化剂和自由基清除剂。在本研究中，我们揭示了褪黑素在减轻鸡模型中砷和氟化物诱导的心脏损伤方面具有巨大的治疗潜力。总共72只1日龄的雄性海兰褐肉鸡被随机分为八组：对照组（基础日粮）、砷组（日粮中含36 mg/kg AsO）、氟组（日粮中含400 mg/kg NaF）、砷 + 氟组（日粮中含36 mg/kg AsO和400 mg/kg NaF）、褪黑素组（日粮中含2.5 mg/kg褪黑素）、砷 + 褪黑素组（日粮中含36 mg/kg AsO和2.5 mg/kg褪黑素）、氟 + 褪黑素组（日粮中含400 mg/kg NaF和2.5 mg/kg褪黑素）以及砷 + 氟 + 褪黑素组（日粮中含36 mg/kg AsO、400 mg/kg NaF和2.5 mg/kg褪黑素）。在用砷、氟或其组合进行23周的干预后，鸡表现出明显的心脏损伤和心肌纤维化。血清乳酸脱氢酶（LDH）、天冬氨酸转氨酶（AST）和肌钙蛋白I（cTn-I）水平升高以及组织病理学检查中观察到的明显变化都证明了这一点。日粮中添加褪黑素显著减轻了砷和氟化物诱导的这些心脏损伤。从机制上讲，我们发现褪黑素通过降低氧化应激和细胞凋亡，并通过减轻病理性线粒体分裂、增强线粒体融合和促进线粒体生物发生来恢复线粒体稳态，从而发挥心脏保护作用。总的来说，我们的研究结果突出了褪黑素作为一种有效的心脏保护剂，可对抗砷和氟化物诱导的鸡心脏损伤。
