AUTHOR=Algaidi Sami A. , Faddladdeen Khadija A. , Alrefaei Ghadeer I. , Qahl Safa H. , Albadawi Emad A. , ALmohaimeed Hailah M. , Ayuob Nasra N. 

TITLE=Thymoquinone protects the testes of hypothyroid rats by suppressing pro-inflammatory cytokines and oxidative stress and promoting SIRT1 testicular expression

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1040857

DOI=10.3389/fphar.2022.1040857

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Hypothyroidism has been linked to many testicular structural and dysfunctional changes in males. Thymoquinone (TQ) has shown a potent testicular protective effect through its antioxidant, anti-inflammatory, antiapoptotic, fertility-enhancing, and endocrine modulatory activities.</p><p><bold>Objectives:</bold> This study aimed to investigate the efficacy of TQ in preserving the testicular structure of a model of experimentally induced hypothyroidism in rats and identify the mechanism behind this effect.</p><p><bold>Materials and methods:</bold> Propylthiouracil (PTU) was used to induce hypothyroidism in adult male Wistar rats, who were then treated with TQ (50 mg/kg/body weight) for 4 weeks and compared to the untreated rats. Thyroid hormonal profile, oxidants/antioxidants profile, and serum testosterone levels were assessed. Gene expression and immune expression of SIRT1 and pro-inflammatory cytokines TNF-α and NF-κB were also assessed in the testicular tissue.</p><p><bold>Results:</bold> TQ administration successfully improved PTU-induced disturbance in the thyroid hormonal profile (T3, T4, and TSH), serum testosterone level, and pancreatic antioxidants compared to the untreated hypothyroid group. TQ significantly downregulated (<italic>p</italic> = 0.001, <italic>p</italic> ˂ 0.001) TNF-α and NF-κB transcription, while it significantly upregulated (<italic>p</italic> = 0.01) SIRT1 transcription in the testes of hypothyroid rats. TQ markedly relieved the histopathological testicular changes induced by PTU and significantly increased (<italic>p</italic> = 0.002, <italic>p</italic> = 0.01) the sectional area of seminiferous tubules and germinal epithelial height, respectively. TUNEL-positive apoptotic germinal cells were significantly decreased (<italic>p</italic> ˂ 0.001), while PCNA-positive proliferating germinal cells and androgen receptor expression were significantly increased (<italic>p</italic> ˂ 0.001) in the testes of TQ-treated hypothyroid rats.</p><p><bold>Conclusion:</bold> Thymoquinone could limit the hypothyroidism-induced structural changes in the testis, mostly through the upregulation of SIRT1 expression, which seems to mediate its promising antioxidant, anti-inflammatory and antiapoptotic effects that were evident in this study. Therefore, TQ is recommended as an adjuvant safe supplement in managing hypothyroidism, especially in males.</p>