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

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Abstract

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.

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Acknowledgements

We are appreciative to the Biology Department staff at Ibn Tofail University’s Faculty of Science for their technical support. In addition, the authors would like to express their heartfelt and deepest condolences to the family and friends of Prof. Ali Ouichou, for his loss. The neuroscience family in Morocco will miss one of its significant members, and the University Ibn Tofail has lost a great academic professor, who has contributed to the growth of the neuroscience community in Morocco.

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Mouloud Lamtai, Hajar Benmhammed, and Sofia Azirar performed the experiments, analyzed the data, and wrote the paper. Ayoub Rezqaoui, Oussama Zghari, and Yassine Chahirou participated in behavioral analysis and statistical significance. Abdelghafour El Hamzaoui, Mohamed Yassine El Brouzi, Samir Bikri, and Abdelhalem Mesfioui reviewed and provided comments on the content and interpretation of the manuscript. Aboubaker El Hessni supervised the work and revised and approved the manuscript.

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Correspondence to Mouloud Lamtai.

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Lamtai, M., Benmhammed, H., Azirar, S. et al. Subchronic Exposure to Mixture of Cadmium, Copper, and Nickel Induces Neurobehavioral Deficits and Hippocampal Oxidative Stress of Wistar Rats. Biol Trace Elem Res (2024). https://doi.org/10.1007/s12011-024-04166-9

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