Melatonin is a Neuroprotective and Antioxidant Agent against Neurotoxicity Induced by an Intrahippocampal Injection of Nickel in Rats.

The investigation into the hippocampal function and its response to heavy metal exposure is crucial for understanding the mechanisms underlying neurotoxicity, this can potentially inform strategies for mitigating the adverse effects associated with heavy metal exposure. Melatonin is an essential neuromodulator known for its efficacy as an antioxidant. In this study, we aimed to determine whether melatonin could protect against Nickel (Ni) neurotoxicity. To achieve this, we performed an intracerebral injection of Ni (300 µM NiCl2) into the right hippocampus of male Wistar rats, followed by melatonin treatment. Based on neurobehavioral and neurobiochemical assessments, our results demonstrate that melatonin efficiently enhances Ni-induced behavioral dysfunction and cognitive impairment. Specifically, melatonin treatment positively influences anxious behavior, significantly reduces immobility time in the forced swim test (FST), and improves learning and spatial memory abilities. Moreover, neurobiochemical assays revealed that melatonin treatment modulates the Ni-induced alterations in oxidative stress balance by increasing antioxidant enzyme activities, such as superoxide dismutase (SOD) and catalase (CAT). Additionally, we observed that melatonin significantly attenuated the increased levels of lipid peroxidation (LPO) and nitric oxide (NO). In conclusion, the data from this study suggests that melatonin attenuates oxidative stress, which is the primary mechanism responsible for Ni-induced neurotoxicity. Considering that the hippocampus is the main structure involved in the pathology associated with heavy metal intoxication, such as Ni, these findings underscore the potential therapeutic efficacy of melatonin in mitigating heavy metal-induced brain damage.

Subchronic Exposure to Mixture of Cadmium, Copper, and Nickel Induces Neurobehavioral Deficits and Hippocampal Oxidative Stress of Wistar Rats.

The present study was aimed at evaluating the influence of the subchronic exposure of cadmium (Cd), copper (Cu), and nickel (Ni) mixtures on affective behaviors, memory impairment, and oxidative stress (OS) in the hippocampus. Thirty male Wistar rats were divided into 5 equal groups. Group 1 (control) received a saline solution (NaCl 0.9%). Groups 2, 3, and 4 received Cd (0.25 mg/kg), Cu (0.5 mg/kg), and Ni (0.25 mg/kg), respectively, while group 5 received a Cd, Cu, and Ni mixture through intraperitoneal injections for 2 months. After the exposure period, all rats were submitted to behavioral tests. Subsequently, OS markers and histological changes in the rats' hippocampi were assessed. Results showed that a 2-month exposure to the mixtures of metals (MM) has led to higher anxiety-like and depression-like behaviors and cognitive deficits in rats when compared to the control group and the individual metals. Furthermore, the MM induced heightened OS, evidenced by the rise in lipid peroxidation and nitric oxide levels. These effects were accompanied by a decrease in superoxide dismutase and catalase activities in the hippocampus. The histopathological analysis also supported that MM caused a neuronal loss in the CA3 sub-region. Overall, this study underscores that subchronic exposure to the Cd, Cu, and Ni mixture induces an OS status and histological changes in the hippocampus, with important affective and cognitive behavior variations in rats.

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.

Potential Role of Oxidative Stress in the Effects of Chronic Administration of Iron on Affective and Cognitive Behavior on Male Wistar Rat.

In this work, we studied the impact of chronic iron exposure, in the form of iron sulfate (FeSo4), on affective and cognitive disorders and oxidative stress in the male Wistar rat. The treatment was carried out for 8 weeks, the rats received an intraperitoneal injection of iron at different doses: 0.25, 0.5, and 1 mg/kg. Affective and cognitive disorders are assessed in open field test (OFT), elevated plus maze (EPM), forced swimming test (FST), Morris water maze (MWM), and Y-maze. The hippocampus and prefrontal cortex of each animal were taken for biochemical examination. Our results show that iron exerts anxiogenic and depressogenic effects, which were observed first at the dose of 0.5 mg/kg and continued in a dose-dependent manner up to the maximum tested dose of 1 mg/kg. According to results from the MWM and Y-maze tests, continuous exposure to iron induces cognitive disorders that are defined by the disturbance of working memory and influences spatial learning performance causing a deficit of spatial memory retention. We noted that chronic exposure to iron can be associated with the appearance of a state of oxidative stress in the hippocampus and the prefrontal cortex demonstrated by an increase in lipid peroxidation, an increase in nitric oxide, and also by disturbances in the antioxidant defense systems following a determination of the concentrations of catalase. In conclusion, we can deduce from this work that chronic iron exposure can be related to the induction of cognitive and affective disorders and oxidative stress.