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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

In vitro Pretreatment with Zinc Alleviates the Adverse Effects of Tetrahydrocannabinol on Cultured Mouse Sertoli Cells: Role of Anti-apoptotic and Antioxidant Activities

Author(s): Kimia Ahmadi, Fatemeh Asgharzadeh, Shadi Mohammadpour-Asl, Fatemeh Ayari, Fatemeh Rahbar, Morteza Motazakker, Shiva Roshan-Milani and Amin Abdollahzade Fard*

Volume 23, Issue 13, 2023

Published on: 15 June, 2023

Page: [1611 - 1620] Pages: 10

DOI: 10.2174/1871530323666230322092046

Price: $65

Abstract

Background: Global rise in cannabis abuse during reproductive years has placed a large number of men at risk for the adverse consequences of δ-9-tetrahydrocannabinol (THC), the primary active component of cannabis. It has been reported that THC affects male fertility and causes testicular cell dysfunction and apoptosis. This study aimed to investigate the possible protective role of zinc pretreatment against the toxic effects of THC in cultured mouse Sertoli cells and the underlying mechanism.

Methods: The Mus Musculus Sertoli cell line (TM4) was cultured, exposed to THC alone (470 μM, 24 h), co-administered with zinc (8 μM, 48 h), and investigated in three groups: control, THC, and THC + zinc. The MTT was performed to evaluate cell viability. TUNEL assay was also applied for the detection of cell apoptosis and a western blot was performed for measuring protein expression levels of Caspase3, Pro-caspase3, SOD, and PDGF-A.

Results: THC significantly decreased cell viability (p < 0.001) and expression levels of SOD, PDGF-A, and pro-caspase3 proteins (p < 0.05 for all), whereas increased Sertoli cells apoptosis (p < 0.001) and expression level of cleaved caspase3 protein (p < 0.001). Pretreatment with zinc reversed THC-induced apoptotic and oxidative effects and reduced cleaved caspase3/pro-caspase3 ratio but could not reverse THC-induced reduction of PDGF-A expression level in TM4 cells.

Conclusion: The present data suggest that THC induces Sertoli cell damage through a multitarget mechanism. Zinc was reported to protect against THC-induced Sertoli cell damage due to its antiapoptotic and antioxidant activities, indicating its clinical importance against THC-induced testicular toxicity among addicted men.

Keywords: Apoptosis, caspase 3, PDGF-A, sertoli cell, SOD, tetrahydrocannabinol, zinc.

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