Department of Clinical Pharmacy, Faculty of Pharmacy, Misr International University, Km 28, Cairo-Ismailia road, PO Box 1, Heliopolis, Cairo, Egypt.
Department of Physiology, Faculty of Medicine for Girls (Cairo), Al-Azhar University, Cairo, Egypt.
BMC Complement Altern Med. 2018 Sep 17;18(1):255. doi: 10.1186/s12906-018-2272-z.
The male reproductive system is a sensitive and intricate process that can be distressed following exposure to various toxicants. Therapeutic drugs, especially chemotherapeutics, can also adversely affect male fertility by instigating hormonal changes leading to testicular cells injury. Azathioprine (AZA) is an effective anticancer drug, but some cases of testicular toxicity have been reported. The aim of this work was to investigate the protective effects of taurine chloramine (TAU-Cl), a reported antioxidant and antiinflammtory peptide, against AZA-induced testicular dysfunction in male rats and ascertain the contributing mechanisms.
Forty male rats were allocated into four equal groups; (i) normal control rats, (ii) TAU-Cl group (100 mg/kg b.w/day for 10 weeks, (iii) AZA group (5 mg/day for 4 weeks); (iv) TAU-Cl/AZA group.
AZA caused increased DNA damage in the testes, and alterations in sex hormones and sperm quality, including sperm count, viability, and motility. Moreover, testicular tissue from the AZA-treated group had increased levels of oxidative stress indicator, MDA, and decreased activity of the antioxidant enzymes as superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) levels. These deleterious events were accompanied by upregulated levels of the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and protein expression of iNOS and NFκB-p65, interleukin-1beta (IL-1β), and proapoptotic marker; caspase-9, together with decreased Bcl-2, NrF2 and hemeoxygenase (HO-1) expression. In contrast, TAU-Cl pretreatment significantly abrogated these toxic effects which were confirmed histologically.
Pretreatment with TAU-Cl exerts a protective effect against AZA-induced male reproductive testicular atrophy. This finding could open new avenues for the use of TAU-Cl as a complementary approach to chemotherapy supportive care.
男性生殖系统是一个敏感而复杂的过程，接触各种毒物后可能会受到损害。治疗药物，特别是化疗药物，通过引发导致睾丸细胞损伤的激素变化，也会对男性生育力产生不利影响。硫唑嘌呤（AZA）是一种有效的抗癌药物，但已有报道称其会引起睾丸毒性。本研究旨在探讨牛磺酸氯胺（TAU-Cl）作为一种抗氧化和抗炎肽，对雄性大鼠 AZA 诱导的睾丸功能障碍的保护作用，并确定其作用机制。
将 40 只雄性大鼠随机分为 4 组：（i）正常对照组，（ii）TAU-Cl 组（100mg/kg b.w/day，连续 10 周），（iii）AZA 组（5mg/day，连续 4 周），（iv）TAU-Cl/AZA 组。
AZA 导致睾丸 DNA 损伤增加，以及性激素和精子质量发生改变，包括精子计数、活力和运动能力。此外，AZA 处理组的睾丸组织中氧化应激标志物 MDA 水平升高，抗氧化酶超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）和过氧化氢酶（CAT）活性降低。这些有害事件伴随着促炎细胞因子肿瘤坏死因子-α（TNF-α）和诱导型一氧化氮合酶（iNOS）和核因子 κB-p65（NFκB-p65）、白细胞介素-1β（IL-1β）和促凋亡标志物；半胱天冬酶-9 的蛋白表达水平升高，同时 Bcl-2、NrF2 和血红素加氧酶（HO-1）的表达水平降低。相反，TAU-Cl 预处理显著阻断了这些毒性作用，这在组织学上得到了证实。
TAU-Cl 预处理对 AZA 诱导的雄性生殖系统睾丸萎缩具有保护作用。这一发现为将 TAU-Cl 作为化疗支持治疗的补充方法开辟了新的途径。
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