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山柰酚通过激活 Nrf-2/Keap-1 通路对聚乙烯微塑料诱导的睾丸损伤的缓解潜力。

Mitigative potential of kaempferide against polyethylene microplastics induced testicular damage by activating Nrf-2/Keap-1 pathway.

机构信息

Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad 38040, Pakistan.

Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad 38040, Pakistan.

出版信息

Ecotoxicol Environ Saf. 2024 Jan 1;269:115746. doi: 10.1016/j.ecoenv.2023.115746. Epub 2023 Nov 29.

Abstract

Polyethylene microplastics (PE-MPs) are one of the environmental contaminants that instigate oxidative stress (OS) in various organs of the body, including testes. Kaempferide (KFD) is a plant-derived natural flavonol with potential neuroprotective, hepatoprotective, anti-cancer, anti-oxidant and anti-inflammatory properties. Therefore, the present study was designed to evaluate the alleviative effects of KFD against PE-MPs-prompted testicular toxicity in rats. Fourty eight adult male albino rats were randomly distributed into 4 groups: control, PE-MPs-administered (1.5 mgkg), PE-MPs (1.5 mgkg) + KFD (20 mgkg) co-treated and KFD (20 mgkg) only treated group. PE-MPs intoxication significantly (P < 0.05) lowered the expression of Nrf-2 and anti-oxidant enzymes, while increasing the expression of Keap-1. The activities of anti-oxidants i.e., catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), hemeoxygene-1 (HO-1) and glutathione peroxidase (GPx) were reduced, besides malondialdehyde (MDA) and reactive oxygen species (ROS) contents were increased significantly (P < 0.05) following the PE-MPs exposure. Moreover, PE-MPs exposure significantly (P < 0.05) reduced the sperm motility, viability and count, whereas considerably (P < 0.05) increased the dead sperm number and sperm structural anomalies. Furthermore, PE-MPs remarkably (P < 0.05) decreased steroidogenic enzymes and Bcl-2 expression, while increasing the expression of Caspase-3 and Bax. PE-MPs exposure significantly (P < 0.05) reduced the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone, whereas inflammatory indices were increased. PE-MPs exposure also induced significant histopathological damages in the testes. Nevertheless, KFD supplementation significantly (P < 0.05) abrogated all the damages induced by PE-MPs. The findings of our study demonstrated that KFD could significantly attenuate PE-MPs-instigated OS and testicular toxicity, due to its anti-oxidant, anti-inflammatory, androgenic and anti-apoptotic potential.

摘要

聚乙烯微塑料 (PE-MPs) 是引发体内各种器官氧化应激 (OS) 的环境污染物之一,包括睾丸。山柰酚 (KFD) 是一种植物源性天然类黄酮,具有潜在的神经保护、肝保护、抗癌、抗氧化和抗炎特性。因此,本研究旨在评估 KFD 对 PE-MPs 引起的大鼠睾丸毒性的缓解作用。48 只成年雄性白化大鼠随机分为 4 组:对照组、PE-MPs 给药组(1.5mg/kg)、PE-MPs(1.5mg/kg)+KFD(20mg/kg)联合治疗组和 KFD(20mg/kg)单独治疗组。PE-MPs 中毒显著(P<0.05)降低了 Nrf-2 和抗氧化酶的表达,同时增加了 Keap-1 的表达。抗氧化剂活性,即过氧化氢酶 (CAT)、谷胱甘肽还原酶 (GSR)、超氧化物歧化酶 (SOD)、血红素加氧酶-1 (HO-1) 和谷胱甘肽过氧化物酶 (GPx) 的活性降低,此外丙二醛 (MDA) 和活性氧 (ROS) 含量显著增加(P<0.05)PE-MPs 暴露后。此外,PE-MPs 暴露显著(P<0.05)降低了精子的活力、活力和计数,而显著增加了死精子数量和精子结构异常。此外,PE-MPs 显著(P<0.05)降低了甾体生成酶和 Bcl-2 的表达,同时增加了 Caspase-3 和 Bax 的表达。PE-MPs 暴露显著(P<0.05)降低了促卵泡激素 (FSH)、促黄体生成素 (LH) 和睾酮的水平,而炎症指数增加。PE-MPs 暴露还导致睾丸组织学损伤。然而,KFD 补充剂显著(P<0.05)减轻了 PE-MPs 引起的所有损伤。本研究结果表明,KFD 可通过其抗氧化、抗炎、雄激素和抗凋亡作用,显著减轻 PE-MPs 引起的 OS 和睾丸毒性。

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