Melatonin mitigates arsenic and fluoride-induced cardiotoxicity in chickens by maintaining mitochondrial homeostasis

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 altera...

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Main Authors: Xiaohong Yuan, Bokai Wen, Xin Hu, Mingyu Yang, Liqun Han, Shengjie Zhao, Jianhai Zhang, Yanqin Ma
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Poultry Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S0032579125005681
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author Xiaohong Yuan
Bokai Wen
Xin Hu
Mingyu Yang
Liqun Han
Shengjie Zhao
Jianhai Zhang
Yanqin Ma
author_facet Xiaohong Yuan
Bokai Wen
Xin Hu
Mingyu Yang
Liqun Han
Shengjie Zhao
Jianhai Zhang
Yanqin Ma
author_sort Xiaohong Yuan
collection DOAJ
description 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 As2O3 in diet), Fluoride Group (400 mg/kg NaF in diet), Arsenic + Fluoride Group (36 mg/kg As2O3 and 400 mg/kg NaF in diet), Melatonin Group (2.5 mg/kg melatonin in diet), Arsenic + Melatonin Group (36 mg/kg As2O3 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 As2O3, 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.
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series Poultry Science
spelling doaj-art-5589a9b4b52744f2b83f9598e81bee892025-08-20T03:51:30ZengElsevierPoultry Science0032-57912025-08-01104810532510.1016/j.psj.2025.105325Melatonin mitigates arsenic and fluoride-induced cardiotoxicity in chickens by maintaining mitochondrial homeostasisXiaohong Yuan0Bokai Wen1Xin Hu2Mingyu Yang3Liqun Han4Shengjie Zhao5Jianhai Zhang6Yanqin Ma7College of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi, 030801, ChinaCollege of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi, 030801, ChinaCollege of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi, 030801, ChinaCollege of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi, 030801, ChinaCollege of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi, 030801, ChinaCollege of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi, 030801, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, ChinaCollege of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi, 030801, China; Corresponding author.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 As2O3 in diet), Fluoride Group (400 mg/kg NaF in diet), Arsenic + Fluoride Group (36 mg/kg As2O3 and 400 mg/kg NaF in diet), Melatonin Group (2.5 mg/kg melatonin in diet), Arsenic + Melatonin Group (36 mg/kg As2O3 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 As2O3, 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.http://www.sciencedirect.com/science/article/pii/S0032579125005681ArsenicFluorideMelatoninHeartMitochondrial homeostasis
spellingShingle Xiaohong Yuan
Bokai Wen
Xin Hu
Mingyu Yang
Liqun Han
Shengjie Zhao
Jianhai Zhang
Yanqin Ma
Melatonin mitigates arsenic and fluoride-induced cardiotoxicity in chickens by maintaining mitochondrial homeostasis
Poultry Science
Arsenic
Fluoride
Melatonin
Heart
Mitochondrial homeostasis
title Melatonin mitigates arsenic and fluoride-induced cardiotoxicity in chickens by maintaining mitochondrial homeostasis
title_full Melatonin mitigates arsenic and fluoride-induced cardiotoxicity in chickens by maintaining mitochondrial homeostasis
title_fullStr Melatonin mitigates arsenic and fluoride-induced cardiotoxicity in chickens by maintaining mitochondrial homeostasis
title_full_unstemmed Melatonin mitigates arsenic and fluoride-induced cardiotoxicity in chickens by maintaining mitochondrial homeostasis
title_short Melatonin mitigates arsenic and fluoride-induced cardiotoxicity in chickens by maintaining mitochondrial homeostasis
title_sort melatonin mitigates arsenic and fluoride induced cardiotoxicity in chickens by maintaining mitochondrial homeostasis
topic Arsenic
Fluoride
Melatonin
Heart
Mitochondrial homeostasis
url http://www.sciencedirect.com/science/article/pii/S0032579125005681
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