Evaluating the Protective Effects of Melatonin Against Chronic Iron Administration in Male Wistar Rats: a Comparative Analysis of Affective, Cognitive, and Oxidative Stress with EDTA Chelator

Iron is the dominant metal in the brain and is distributed widely. However, it can lead to various neuropathological and neurobehavioral abnormalities as well as oxidative stress. On the other hand, melatonin, a pineal hormone, is known for its neuroprotective properties, as well as its ability to act as a natural chelator against oxidative stress. It has also been used as an antidepressant and anxiolytic. The study investigated the potential of melatonin and EDTA treatment to prevent anxiety, depressive behavior, and memory impairment in male rats induced by chronic iron administration, and its connection to oxidative stress regulation in the hippocampus and prefrontal cortex. The rats were divided into six groups and intraperitoneally injected for 8 weeks with NaCl solution (control), iron sulfate (1 mg/kg), melatonin (4 mg/kg), EDTA (4 mg/kg), 1 mg/kg of iron + 4 mg/kg of melatonin, or 1 mg/kg of iron + 4 mg/kg of EDTA. In this study, we performed a neurobehavioral assessment and biochemical determinations of oxidative stress levels in the hippocampus and prefrontal cortex of each animal. The results indicate that chronic exposure to iron sulfate induced anxiety-like depressive behavior, and cognitive impairment also increased the levels of lipid peroxidation and nitric oxide, and reduced the activity of catalase in the hippocampus and prefrontal cortex in male Wistar rats, suggesting the induction of oxidative stress. In contrast, these alterations were reversed by melatonin better than EDTA. The results of this study show that melatonin protects against the neurobehavioral changes caused by iron, which may be associated with decreasing oxidative stress in the hippocampus and prefrontal cortex.