Melatonins paradox: From therapeutic benefits to toxicity warnings
Amrollahi-Sharifabadi M. Oladejo T.O. Ibrahim A.S. Shakoor B. Mehrpour O. Sadeghi-Hashjin G. Gonçalves S.
25 August 2025Elsevier Ireland Ltd
Chemico-Biological Interactions
2025#417
Melatonin is an endogenous chemical predominantly synthesized in the pineal gland, widely recognized for its hormonal roles, such as regulating sleep and circadian rhythms. Through mechanisms such as anti-oxidative reduction, anti-inflammatory, and immunomodulation, it is suggested that melatonin exhibits biochemical properties in in vitro conditions. Beyond these functions, melatonin has garnered attention for its pharmacological benefits, particularly as a therapeutic agent that is exogenously administered as a supplement in various diseases ranging from insomnia to immunological and gastrointestinal disorders. However, emerging studies highlight potential toxicological concerns associated with exogenous melatonin use, especially in specific populations. This review provided a comprehensive exploration of melatonins dual role as a therapeutic and potentially toxic agent. It summarized what is currently known about its pharmacological, toxicological, and biochemical characteristics as well as toxicity mechanisms, and safety concerns in susceptible groups. By highlighting new knowledge gaps about melatonins clinical uses, the study opens the door for further studies to maximize its therapeutic benefits while maintaining its safety.
Biochemistry , Mechanism of action , Melatonin , Pharmacology , Safety profile , Toxicology
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Department of Basic Sciences, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, 68151-44316, Iran
Department of Pharmacology and Toxicology, Nazarbayev School of Medicine, Astana, Kazakhstan
Synthetic and Natural Product Drug Discovery Laboratory, Department of Chemistry, Government College Women University Faisalabad, Faisalabad, 38000, Pakistan
Michigan Poison & Drug Information Center, School of Medicine, Wayne State University, Detroit, MI, United States
Department of Comparative Biosciences, College of Veterinary Medicine & Biomedical Science, University of Tehran, Tehran, Iran
Academic Clinical Center of Trás-os-Montes and Alto Douro (CACTMAD), University of Trás-os-Montes and Alto Douro, Vila Real, 5000-801, Portugal
School of Health, University of Trás-os-Montes and Alto Douro, Vila Real, 5000-801, Portugal
Department of Basic Sciences
Department of Pharmacology and Toxicology
Synthetic and Natural Product Drug Discovery Laboratory
Michigan Poison & Drug Information Center
Department of Comparative Biosciences
Academic Clinical Center of Trás-os-Montes and Alto Douro (CACTMAD)
School of Health
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