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Review
. 2025 Aug 25:417:111556.
doi: 10.1016/j.cbi.2025.111556. Epub 2025 May 16.

Melatonin's paradox: From therapeutic benefits to toxicity warnings

Affiliations
Review

Melatonin's paradox: From therapeutic benefits to toxicity warnings

Mohammad Amrollahi-Sharifabadi et al. Chem Biol Interact. .

Abstract

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 melatonin's 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 melatonin's clinical uses, the study opens the door for further studies to maximize its therapeutic benefits while maintaining its safety.

Keywords: Biochemistry; Mechanism of action; Melatonin; Pharmacology; Safety profile; Toxicology.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare that there are no conflicts of/or competing interests.

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