Melatonin Ameliorates Cadmium-Induced Affective and Cognitive Impairments and Hippocampal Oxidative Stress in Rat


The present work aims to evaluate the effect of melatonin (Mel) on affective and cognitive disorders induced by chronic exposure to Cadmium (Cd). Male and female Wistar rats received either an intraperitoneal injection of saline solution NaCl (0.9%), Mel (4 mg/kg), Cd (1 mg/kg), or Cd (1 mg/kg) + Mel (4 mg/kg) for 8 weeks. Behavioral disorders were evaluated by different tests mainly the open field and elevated plus maze tests for anxiety-like behavior, forced swimming test (FST) for depression-like behavior, and the Y-maze and Morris water maze (MWM) tests for cognitive disorders. Thereafter, oxidative stress indices and histology of the hippocampus were evaluated. The results confirm that Cd administration has anxiogenic-like effects in both anxiety tests and depressive-like effects in the FST and leads to memory and learning disabilities in the Y-maze and MWM. We also report that Mel counteracts these neurobehavioral disorders. Biochemical assays showed that rats intoxicated with Cd significantly increased levels of nitric oxide (NO) and lipid peroxidation (LPO), while the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly decreased in the hippocampus. In contrast, Mel administration attenuates the Cd-induced changes. The histopathological studies in the hippocampus of rats also supported that Mel markedly reduced the Cd-induced neuronal loss in CA3 sub-region. Overall, our results suggest that Mel could be used to protect against Cd-induced neurobehavioral changes via its antioxidant properties in the hippocampus. The effects of Cd and Mel are sex-dependent, knowing that Cd is more harmful in males, while Mel is more protective in females.

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Mouloud Lamtai and Sofia Azirar performed the experiments, analyzed the data and wrote the paper. Sihame Ouakki and Oussama Zghari participated in behavioral analysis and statistical significance. Abdelhalem Mesfioui and Aboubaker El Hessni reviewed and provided comments on the content and interpretation of the manuscript. Ali Ouichou supervised the work, revised and approved the manuscript

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Correspondence to Mouloud Lamtai.

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Lamtai, M., Azirar, S., Zghari, O. et al. Melatonin Ameliorates Cadmium-Induced Affective and Cognitive Impairments and Hippocampal Oxidative Stress in Rat. Biol Trace Elem Res 199, 1445–1455 (2021).

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  • Cadmium
  • Melatonin
  • Anxiety-like
  • Depression-like
  • Memory
  • Oxidative stress