Osama Hadeel M, Khadrawy Sally M, El-Nahass El-Shaymaa, Othman Sarah I, Mohamed Hanaa M
Genetics and Molecular Biology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
Pathology Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt.
Lab Anim Res. 2024 May 14;40(1):19. doi: 10.1186/s42826-024-00204-8.
Thyroid hormones (THs) regulate growth, development and function of different tissues. Hypothyroidism is a common clinical disorder characterized by deficiency in THs and adversely affects the development and functions of several organs. This work aimed to investigate the ameliorative effect of eltroxin (ELT), a hypothyroidism medication, and hesperidin (HSP), a flavonoid, against testicular and renal toxicity in hypothyroid rats. Twenty-four rats were divided into four groups and treated orally for 12 weeks. Group I (control), group II (hypothyroidism) received 20 mg/kg carbimazole (CBZ), group III received CBZ and 0.045 mg/kg ELT, and group IV received CBZ and 200 mg/kg HSP.
CBZ administration induced biochemical and histopathological changes in testis and kidney. Co-administration of ELT or HSP significantly (P < 0.05) ameliorated THs, reduced urea and creatinine while raised follicle stimulating hormone (FSH), Luteinizing hormone (LH), and testosterone in serum. Testicular and renal malondialdehyde level as a lipid peroxidation indicator, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly (P < 0.05) decreased while glutathione content, glutathione peroxidase, and glutathione-s-transferase activities were significantly (P < 0.05) increased. The histopathological changes were also diminished. Decreased mRNA and protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and peroxisome proliferator-activated receptor gamma(PPARγ) in hypothyroid rats were up-regulated after ELT or HSP treatment.
ELT and HSP showed antioxidant and anti-inflammatory effects against CBZ-induced testicular and renal toxicity, and these effects may be promoted via activating Nrf2/HO-1 and PPARγ signaling pathways.
甲状腺激素（THs）调节不同组织的生长、发育和功能。甲状腺功能减退症是一种常见的临床疾病，其特征为甲状腺激素缺乏，并对多个器官的发育和功能产生不利影响。本研究旨在探讨左旋甲状腺素（ELT，一种治疗甲状腺功能减退症的药物）和橙皮苷（HSP，一种类黄酮）对甲状腺功能减退大鼠睾丸和肾脏毒性的改善作用。将24只大鼠分为四组，并进行为期12周的口服治疗。第一组（对照组），第二组（甲状腺功能减退组）接受20mg/kg甲巯咪唑（CBZ），第三组接受CBZ和0.045mg/kg ELT，第四组接受CBZ和200mg/kg HSP。
给予CBZ可引起睾丸和肾脏的生化及组织病理学变化。联合给予ELT或HSP可显著（P<0.05）改善甲状腺激素水平，降低尿素和肌酐水平，同时提高血清中的促卵泡生成素（FSH）、黄体生成素（LH）和睾酮水平。作为脂质过氧化指标的睾丸和肾脏丙二醛水平、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）显著（P<0.05）降低，而谷胱甘肽含量、谷胱甘肽过氧化物酶和谷胱甘肽-S-转移酶活性显著（P<0.05）升高。组织病理学变化也有所减轻。甲状腺功能减退大鼠中核因子红细胞2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）和过氧化物酶体增殖物激活受体γ（PPARγ）的mRNA和蛋白表达降低，经ELT或HSP治疗后上调。
ELT和HSP对CBZ诱导的睾丸和肾脏毒性具有抗氧化和抗炎作用，这些作用可能通过激活Nrf2/HO-1和PPARγ信号通路来促进。
