1. Protective Effects of Co-administration of Zinc and Selenium Against Streptozotocin-Induced Alzheimer's Disease: Behavioral, Mitochondrial Oxidative Stress, and GPR39 Expression Alterations in Rats.
- Author
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Farbood Y, Sarkaki A, Mahdavinia M, Ghadiri A, Teimoori A, Seif F, Dehghani MA, and Navabi SP
- Subjects
- Alzheimer Disease chemically induced, Alzheimer Disease physiopathology, Animals, Brain metabolism, Catalase drug effects, Catalase metabolism, Gene Expression drug effects, Glutathione Peroxidase drug effects, Glutathione Peroxidase metabolism, Lipid Peroxidation drug effects, Mitochondria drug effects, Mitochondria metabolism, Rats, Reactive Oxygen Species, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Streptozocin toxicity, Superoxide Dismutase drug effects, Superoxide Dismutase metabolism, Alzheimer Disease metabolism, Brain drug effects, Cognition drug effects, Neuroprotective Agents pharmacology, Oxidative Stress drug effects, Receptors, G-Protein-Coupled drug effects, Selenium pharmacology, Zinc pharmacology
- Abstract
Changes in the concentrations of trace metals such as zinc (Zn) and selenium (Se) can pathologically lead to neurodegenerative conditions such as the Alzheimer's disease (AD). Previous studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of AD. Several male Wistar rats were randomly divided into five groups: sham group, AD group that received 3 mg/kg of streptozotocin (STZ) intracerebroventricularly, AD + Zn group that received 10 mg/kg of Zn intraperitoneally (i.p.) for 1 week, AD + Se group that received 0.1 mg/kg of Se i.p. for 1 week, and AD + Zn + Se group that received 10 mg/kg of Zn i.p. plus 0.1 mg/kg of Se i.p. for 1 week. At end of the study, behavioral tests and mitochondrial oxidative stress and GPR39 gene expression evaluations were carried out. Co-administration of Zn and Se significantly decreased the potential collapse of mitochondrial membrane, reactive oxygen species levels, and lipid peroxidation levels while significantly increased cognitive performance, superoxide dismutase (SOD), glutathione peroxidase, and catalase activity in the brain mitochondria compared with the STZ group. In addition, no significant changes were observed in GPR39 expression in the co-treated group. Findings of the current study showed that ZnR/GPR39 receptor, mitochondrial dysfunction, and oxidative stress play important roles in the pathogenesis of AD. Co-treatment of Zn and Se improved the cognitive performance, mitochondrial dysfunction, and oxidative stress caused by STZ-induced AD. Therefore, therapeutic approaches to improve mitochondrial function could be effective in preventing the initiation and progression of AD.
- Published
- 2020
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