Lead (Pb) is a toxic heavy metal that is harmful to humans, especially male reproductive organs. Luteolin (LUT) is a naturally occurring flavonoid with numerous biological activities. Our aim was to investigate the possible reproprotective effect of LUT against testicular deficits induced by Pb intoxication. In the present study, 28 rats were distributed into 4 groups: control, LUT (50 mg/kg), lead acetate (PbAc, 20 mg/kg), and LUT + PbAc groups, in which rats were pre‐treated with LUT 3 hr before PbAc injection. All animals were treated for 7 days. Oxidative stress, inflammatory and apoptotic markers along with histopathological changes have been examined using spectrophotometric, ELISA, real‐time PCR, and histopathological methods. PbAc injection elevated Pb concentration in testicular tissue and decreased levels of sex hormones. PbAc intoxication exacerbated lipoperoxidation and nitric oxide formation, depleted superoxide dismutase, and catalase activities along with glutathione and its originated enzymes (glutathione peroxidase and glutathione reductase). At the molecular level, PbAc deactivated nuclear factor erythroid 2‐related factor 2 and heme oxygenase‐1 in the testicular tissue. In addition, PbAc toxicity induced inflammatory and apoptotic cascades in testicular tissue as evidenced by the increased tumor necrosis factor‐alpha, interleukin‐1 beta, inducible nitric oxide synthase, Bax, and caspase 3, while Bcl‐2 was declined. Histopathological examination of testicular tissue also revealed that PbAc caused degeneration alterations in spermatogenic cells, the spermatogenic epithelial cells were disconnected from the basement membrane, and the seminiferous tubules were vacuolated. Remarkably, pre‐treatment with LUT minimized significantly the testicular damage induced by PbAc. Therefore, we conclude that LUT may have a beneficial effect against PbAc‐induced testicular injury through preventing oxidative challenge, inflammation, and finally apoptosis.

中文翻译：

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木犀草素通过激活 Nrf2/HO ‐1 通路防止醋酸铅引起的睾丸损伤

铅 (Pb) 是一种有毒重金属，对人类，尤其是男性生殖器官有害。木犀草素 (LUT) 是一种天然存在的黄酮类化合物，具有多种生物活性。我们的目的是研究 LUT 对铅中毒引起的睾丸缺陷的可能的再保护作用。在本研究中，28 只大鼠被分为 4 组：对照组、LUT（50 mg/kg）、醋酸铅（PbAc，20 mg/kg）和 LUT + PbAc 组，其中大鼠用 LUT 3 预处理PbAc 注射前 hr。所有动物均治疗7天。已经使用分光光度法、ELISA、实时 PCR 和组织病理学方法检查了氧化应激、炎症和凋亡标志物以及组织病理学变化。PbAc 注射提高了睾丸组织中的 Pb 浓度并降低了性激素的水平。PbAc 中毒加剧了脂质过氧化和一氧化氮的形成，耗尽了超氧化物歧化酶和过氧化氢酶活性以及谷胱甘肽及其起源的酶（谷胱甘肽过氧化物酶和谷胱甘肽还原酶）。在分子水平上，PbAc 使睾丸组织中的核因子红细胞 2 相关因子 2 和血红素加氧酶 1 失活。此外，PbAc 毒性在睾丸组织中诱导炎症和细胞凋亡级联反应，如肿瘤坏死因子 α、白细胞介素 1 β、诱导型一氧化氮合酶、Bax 和半胱天冬酶 3 增加所证明，而 Bcl-2 下降。睾丸组织的组织病理学检查也显示 PbAc 引起生精细胞的变性改变，生精上皮细胞与基底膜断开，和生精小管空泡化。值得注意的是，LUT 预处理显着减少了 PbAc 引起的睾丸损伤。因此，我们得出结论，LUT 可能通过防止氧化挑战、炎症和​​最终细胞凋亡对 PbAc 诱导的睾丸损伤产生有益作用。