Chronic copper exposure leads to hippocampus oxidative stress and impaired learning and memory in male and female rats
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Toxicol Res. https://doi.org/10.1007/s43188-020-00043-4
Toxicological Research
ORIGINAL ARTICLE
Chronic copper exposure leads to hippocampus oxidative stress and impaired learning and memory in male and female rats Mouloud Lamtai1 · Oussama Zghari1 · Sihame Ouakki1 · Ilias Marmouzi2 · Abdelhalem Mesfioui1 · Aboubaker El Hessni1 · Ali Ouichou1 Received: 15 December 2019 / Revised: 18 January 2020 / Accepted: 18 February 2020 © Korean Society of Toxicology 2020
Abstract Environmental and occupational exposures to copper (Cu) play a pivotal role in the etiology of some neurological diseases and reduced cognitive functions. However, the precise mechanisms of its effects on cognitive function have not been yet thoroughly established. In our study, we aimed to investigate the behavior and neurochemical alterations in hippocampus of male and female rats, chronically exposed to copper chloride (CuCl2) and the possible involvement of oxidative stress. Twenty-four rats, for each gender, were divided into control and three test groups (n = 6), and were injected intraperitoneally with saline (0.9% NaCl) or CuCl2 (0.25 mg/kg, 0.5 mg/kg and 1 mg/kg) for 8 weeks. After the treatment period, Y-maze test was used for the evaluation of spatial working memory and the Morris Water Maze (MWM) to test the spatial learning and memory. Biochemical determination of oxidative stress levels in hippocampus was performed. The main results of the present work are working memory impairment in spatial Y-maze which induced by higher Cu intake (1 mg/kg) in male and female rats. Also, In the MWM test, the spatial learning and memory were significantly impaired in rats treated with Cu at dose of 1 mg/kg. Additionally, markers of oxidative stress such as catalase, superoxide dismutase, lipid peroxidation products and nitric oxide levels were significantly altered following Cu treatments. These data propose that compromised behavior following Cu exposure is associated with increase in oxidative stress. Keywords Copper · Memory · Oxidative stress · Sex differences · Chronic toxicity
Introduction In our environment, heavy metals are prevalent in air, soil and water. Virtually, they exist everywhere [1]. Among the heavy metals, copper (Cu) is an essential trace mineral which becomes harmful when the safe dose is surpassed [2]. Generally, Cu can ensure the proper functioning of various Work supervisor: Ali Ouichou. * Mouloud Lamtai mouloud‑[email protected] Ali Ouichou [email protected] 1
Laboratory of Genetics, Neuroendocrinology and Biotechnology, Faculty of Science, Ibn Tofail University, BP 133, Kénitra 14000, Morocco
Laboratoire de Pharmacologie et Toxicologie, équipe de Pharmacocinétique, Faculté de Médicine et Pharmacie, University Mohammed V in Rabat, Rabat Instituts, Rabat, Morocco
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biological systems such as the central nervous system (CNS) in different animal species [3–5]. It can regulate several biochemical processes [6, 7] and participates in neurotransmitter synthesis, energy metabolism and antioxidative defense [8]. T
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