Algaidi Sami A, Faddladdeen Khadija A, Alrefaei Ghadeer I, Qahl Safa H, Albadawi Emad A, ALmohaimeed Hailah M, Ayuob Nasra N
Department of Anatomy, College of Medicine, Taibah University, Medina, Saudi Arabia.
Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Front Pharmacol. 2022 Nov 24;13:1040857. doi: 10.3389/fphar.2022.1040857. eCollection 2022.
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. 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. 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. 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 ( = 0.001, ˂ 0.001) TNF-α and NF-κB transcription, while it significantly upregulated ( = 0.01) SIRT1 transcription in the testes of hypothyroid rats. TQ markedly relieved the histopathological testicular changes induced by PTU and significantly increased ( = 0.002, = 0.01) the sectional area of seminiferous tubules and germinal epithelial height, respectively. TUNEL-positive apoptotic germinal cells were significantly decreased ( ˂ 0.001), while PCNA-positive proliferating germinal cells and androgen receptor expression were significantly increased ( ˂ 0.001) in the testes of TQ-treated hypothyroid rats. 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.
甲状腺功能减退症与男性多种睾丸结构和功能障碍变化有关。黑种草醌（TQ）通过其抗氧化、抗炎、抗凋亡、增强生育能力和内分泌调节活性，显示出强大的睾丸保护作用。本研究旨在探讨TQ对实验性诱导的大鼠甲状腺功能减退模型睾丸结构的保护作用，并确定其作用机制。用丙硫氧嘧啶（PTU）诱导成年雄性Wistar大鼠甲状腺功能减退，然后用TQ（50mg/kg体重）治疗4周，并与未治疗的大鼠进行比较。评估甲状腺激素水平、氧化/抗氧化水平和血清睾酮水平。还评估了睾丸组织中SIRT1以及促炎细胞因子TNF-α和NF-κB的基因表达和免疫表达。与未治疗的甲状腺功能减退组相比，给予TQ成功改善了PTU诱导的甲状腺激素水平（T3、T4和TSH）、血清睾酮水平和胰腺抗氧化剂的紊乱。TQ显著下调（P = 0.001，P ˂ 0.001）甲状腺功能减退大鼠睾丸中TNF-α和NF-κB的转录，同时显著上调（P = 0.01）SIRT1的转录。TQ明显减轻了PTU诱导的睾丸组织病理学变化，并分别显著增加（P = 0.002，P = 0.01）生精小管的横截面积和生精上皮高度。在接受TQ治疗的甲状腺功能减退大鼠睾丸中，TUNEL阳性凋亡生精细胞显著减少（P ˂ 0.001），而PCNA阳性增殖生精细胞和雄激素受体表达显著增加（P ˂ 0.001）。黑种草醌可以限制甲状腺功能减退引起的睾丸结构变化，主要是通过上调SIRT1表达，这似乎介导了其在本研究中明显的抗氧化、抗炎和抗凋亡作用。因此，推荐TQ作为治疗甲状腺功能减退症的辅助安全补充剂，尤其是在男性中。
