The protective effect of zinc on morphine-induced testicular toxicity via p53 and Akt pathways: An in vitro and in vivo approach |
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| Institution: | 1. Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran;2. Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran;3. Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran;4. Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran;5. Nephrology and Kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Iran;6. Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran;7. Department of Pathology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran;1. Department of Chemistry, College of Science, University of Kufa, Iraq;2. Clinical Analysis Department, College of Pharmacy, Hawler Medical University, Havalan City, Erbil, Iraq;3. Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;4. Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria;5. IMPACT Strategic Research Centre, Deakin University, PO Box 281, Geelong, VIC, 3220, Australia;1. Departamento de Procesos y Tecnología, Universidad Autónoma Metropolitana Unidad Cuajimalpa, Mexico City, Mexico;2. Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, (CINVESTAV-IPN), Mexico City, Mexico;3. Departamento de Microscopía Electrónica, Instituto Mexicano del Petróleo, Mexico City, Mexico;4. BGR Bundesansalt fur Geowissenschaften und Rohstoffe, Stilleweg 2, D-30655, Hannover, Germany;1. Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil;2. Laboratory of Cell Culture and Cytogenetics, Environment Section, Evandro Chagas Institute, Ananindeua, PA, Brazil;3. School of Dentistry, Federal University of Pará, Belém, PA, Brazil;4. Laboratory of Toxicology, Environment Section, Evandro Chagas Institute, Ananindeua, PA, Brazil;5. Laboratory of Molecular Pharmacology, Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil;1. Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran;2. Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran;3. Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran;4. Department of Anatomical Sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran;5. Cellular and Molecular Research Center, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran;6. Nephrology and Kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Iran;7. Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran;1. Chair and Department of Human Anatomy, Medical University of Lublin, 20-090, Lublin, Poland;2. Department of Biochemistry and Toxicology, Faculty of Animal Sciences and Bioeconomy, University of Life Sciences in Lublin, 20-950, Lublin, Poland;3. Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Department of Biological Function of Food, Tuwima 10, 10-748, Olsztyn, Poland;1. Department of Neurosciences and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran;2. Cognitive Sciences and Behavioral Research Center, Tehran University of Medical Sciences, Tehran, Iran |
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| Abstract: | BackgroundChronic use of morphine is associated with reproductive complications, such as hypogonadism and infertility. While the side effects of morphine have been extensively studied in the testis, much less is known regarding the effects of morphine on Sertoli cells and the effects of zinc on morphine-induced testicular injury as well as their underlying mechanisms. Therefore, the purpose of this study was to investigate the effect of morphine (alone and co-administered with zinc) on cell viability and apoptosis of the testicular (Sertoli) cells as well as the tumor suppressor p53 and phosphorylated-protein kinase B (p-Akt) protein levels in both in vitro and in vivo models.MethodsCultured Sertoli cells were exposed to morphine (23 μM), zinc (8 μM), and zinc prior to morphine and their effects on Sertoli cell viability and apoptosis were investigated. Morphine (3 mg/kg) and zinc (5 mg/kg, 1 h before morphine) were also injected intraperitoneally to rats and then the apoptotic changes in the testis were evaluated.ResultsCell viability and p-Akt protein levels decreased in morphine-treated cells, while apoptosis and p53 protein expression increased in these cells. Pretreatment with zinc recovered morphine-induced apoptotic effects, as well as over-expression of p53 and down-regulation of p-Akt. These findings were supported by a subsequent animal study.ConclusionThe present data indicated the protective effect of zinc against morphine-induced testicular (Sertoli) cell toxicity via p53/Akt pathways in both in vivo and in vitro models and suggested the clinical importance of zinc on infertility among chronic opioid users and addicted men. |
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| Keywords: | Apoptosis Morphine p53 p-Akt Sertoli cell Zinc |
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