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

Affiliation
Department of Anatomy ,College of Medicine ,Taibah University ,Medina ,Saudi Arabia
Algaidi, Sami A.;
Affiliation
Department of Biology ,Faculty of Science ,King Abdulaziz University ,Jeddah ,Saudi Arabia
Faddladdeen, Khadija A.;
Affiliation
Department of Biology ,College of Science ,University of Jeddah ,Jeddah ,Saudi Arabia
Alrefaei, Ghadeer I.;
Affiliation
Department of Biology ,College of Science ,University of Jeddah ,Jeddah ,Saudi Arabia
Qahl, Safa H.;
Affiliation
Department of Anatomy ,College of Medicine ,Taibah University ,Medina ,Saudi Arabia
Albadawi, Emad A.;
Affiliation
Department of Basic Science ,College of Medicine ,Princess Nourah Bint Abdulrahman University ,Riyadh ,Saudi Arabia
ALmohaimeed, Hailah M.;
Affiliation
Department of Medical Histology ,Faculty of Medicine ,Damietta University ,Damietta ,Egypt
Ayuob, Nasra N.

Background: 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. Objectives: 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. Materials and methods: 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. Results: 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 ( p = 0.001, p ˂ 0.001) TNF-α and NF-κB transcription, while it significantly upregulated ( p = 0.01) SIRT1 transcription in the testes of hypothyroid rats. TQ markedly relieved the histopathological testicular changes induced by PTU and significantly increased ( p = 0.002, p = 0.01) the sectional area of seminiferous tubules and germinal epithelial height, respectively. TUNEL-positive apoptotic germinal cells were significantly decreased ( p ˂ 0.001), while PCNA-positive proliferating germinal cells and androgen receptor expression were significantly increased ( p ˂ 0.001) in the testes of TQ-treated hypothyroid rats. Conclusion: 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.

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License Holder: Copyright © 2022 Algaidi, Faddladdeen, Alrefaei, Qahl, Albadawi, ALmohaimeed and Ayuob.

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