Antioxidant Actions of Melatonin: A Systematic Review of Animal Studies

Abstract

Melatonin is an indoleamine with crucial antioxidant properties that are used to combat inflammatory and neoplastic processes, as well as control transplants. However, the clinical applications of melatonin have not yet been fully consolidated in the literature and require in-depth analysis.

Objectives: This study reviewed the literature on the antioxidant properties of melatonin in rat models.

Methods: We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses and used the PubMed, LILACS, and Cochrane databases, Google Scholar, and article references, irrespective of publication time.

Results: Ten articles involving 485 rats were selected, and the effects of melatonin on antioxidant markers were investigated. Melatonin increased superoxide dismutase in nine studies, glutathione peroxidase in seven studies, and catalase in five studies. In contrast, melatonin reduced glutathione in three studies and malonaldehyde in seven of eight studies.

Conclusion: Our findings suggest that melatonin effectively reduces oxidative stress.

Keywords: antioxidant; melatonin; nitrosative stress; oxidative stress; superoxide dismutase.

Figure 1

Risk of bias using the Systematic Review Center for Laboratory Animal Experiments [12,13,14,15,16,17,18,19,20,21].

Figure 2

Flowchart of identification of new studies via databases and records.

Figure 3

Antioxidant action of melatonin on different tissues. The potential antioxidant properties of melatonin may be related to a) the cascade antioxidant signaling independent receptor [Cyclic 3-hydroxymelatonin (C₃OHM); N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK); N1-acetyl-5-methoxykynuramine (AMK)]; b) inflammatory processes [(activator protein 1 (AP-1); hypoxia-inducible factor 1α (HIF-1α); nuclear factor erythroid 2 factor 2 (Nrf2); nuclear factor kappa B (NF-κB)]; c) the apoptotic system (Bcl-2 [B-cell lymphoma 2]); and d) oxidative system stability [reactive oxygen species (ROS)]. All these processes are related to an increase in enzymatic substances (superoxide dismutase [SOD], glutathione peroxidase [GPx], and catalase [CAT]) and a decrease in the lipid peroxidation marker malondialdehyde (MDA) as indicated by the arrows in the figure. Melatonin is an amphiphilic molecule (hydrophilic and lipophilic) that may be capable of diffusing into different tissues. The potential targets of melatonin are the a) liver, brain, cardiovascular system, kidneys, ovaries, and testicles [12,13,14,15,16,17,18,19,20,21].