Protective effect and mechanism of alpha-lipoic acid on lead-induced Sertoli cell damage in rooster testes

Abstract

Objective: To investigate the protective effect of alpha-lipoic acid on lead-induced Sertoli cell injury and its potential molecular mechanisms using primary Sertoli cells from rooster testes.

Methods: Primary Sertoli cells from 6-week-old rooster testes were divided into four goups. They were treated with serum-free DMEM-F12 medium (the control group), 40 μM lead acetate, 100 μM alpha-lipoic acid, or 40 μM lead acetate plus 100 μM alpha-lipoic acid for 24 h, respectively. Cell viability, reactive oxygen species levels (DCFH-DA), antioxidant enzyme activities (catalase, superoxide dismutase), blood-testis barrier-related proteins, nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway components, proliferation/apoptosis markers (Western blot), and related gene expression (qPCR) were analyzed.

Results: Alpha-lipoic acid treatment significantly reduced lead-induced reactive oxygen species (ROS) production by 58.3% compared to the lead acetate group (P<0.05), enhanced catalase activity by 35.8% (P<0.05), and elevated lead-reduced PCNA expression by 47.2% (P<0.05). Lead acetate 40 μM plus 100 μM alpha-lipoic acid significantly increased Nrf2 expression by 78.9% and HO1/NQO1 expression by 97.5% and 89.4%, respectively (P<0.05), significantly upregulated the expression of Bcl2 protein and significantly downregulated Bax protein expression (P<0.05).

Conclusions: Alpha-lipoic acid enhances the antioxidant properties of Sertoli cells by activating the Nrf2 pathway, restores lead-induced excessive autophagy, and inhibits apoptosis, thus alleviating the damage caused by lead in Sertoli cells.

Keywords

Alpha-lipoic acid / Lead / Sertoli cells / Bloodtestis barrier / Nrf2

Conflict of interest statement

The authors declare no competing interests.

Funding

This study was funded by Zhejiang Provincial Natural Science Foundation of China under Grant No. LTGN24C170001, Zhejiang Province Vocational Education Teaching Reform Project jg20230038, Zhejiang Province Education Science Planning Project 2024JCD034, Jinhua Science and Technology Plan Project 2024-2-002.

Authors’ contributions

Junrong Li and Shanli Zhu contributed to the conceptualization of this study. Shanli Zhu developed the methodology and conducted the validation and formal analysis. Nanwei Ye handled the software analysis, investigation, resources, and visualization. Junrong Li and Shanli Zhu were responsible for data curation. Shanli Zhu prepared the original draft of the manuscript. Junrong Li and Fangxiong Shi conducted the writing review and editing. Shanli Zhu provided supervision for the research. Fangxiong Shi managed the project administration. Junrong Li and Fangxiong Shi acquired the funding for this research. All authors have read and agreed to the published version of the manuscript.

Publisher’s Note

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