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鞣花酸和阿魏酸通过调节睾丸中 Nfe2l2、Ppargc1a 和 StAR 的表达来保护砷诱导的雄性生殖毒性。

Ellagic and ferulic acids protect arsenic-induced male reproductive toxicity via regulating Nfe2l2, Ppargc1a and StAR expressions in testis.

机构信息

Reproductive Physiology Laboratory, Animal Physiology Division, ICAR-National Institute of Animal Nutrition and Physiology, Adugodi, Bengaluru 560030, India.

Reproductive Physiology Laboratory, Animal Physiology Division, ICAR-National Institute of Animal Nutrition and Physiology, Adugodi, Bengaluru 560030, India.

出版信息

Toxicology. 2019 Feb 1;413:1-12. doi: 10.1016/j.tox.2018.11.012. Epub 2018 Nov 29.

DOI:10.1016/j.tox.2018.11.012
PMID:30503583
Abstract

Arsenic (As) - induced oxidative stress causes male reproductive toxicity apart from its other generalized systemic effects. Some phytochemicals through their antioxidant properties might help to overcome such toxic effects. The aim of the study was to elucidate the protective role of the selected phytochemicals, ellagic and ferulic acids against the As-induced reproductive toxicity. Forty two healthy male Swiss albino mice were randomly assigned to six groups (each @ n = 7). Group A served as the control, while group B received 200 ppm of As through drinking water. The group C and D mice were administered Per os (P.O) with 50 mg/kg BW of ellagic and ferulic acids, respectively on alternate days. Group E or F received 50 mg of ellagic or ferulic acid + 200 ppm of As for forty days. Ellagic and/ ferulic acid significantly reduced the accumulation of As, protein carbonylation (PC), lipid peroxidation (LPO) in addition to altering the antioxidant enzymes (CAT and SOD) activities, reduced glutathione (GSH) and total antioxidant capacity (TAC) in the testicular tissues. A significantly (p < 0.05) altered sperm functions (viability, functional membrane integrity, Δψ and sperm kinematics like total motility, rapid, progressive motile and type-A (STR > 80%, ALH > 2.5 μm) and testicular damage induced by the As were ameliorated (p < 0.05) by the phytochemical treatments. These phytochemicals due to their antioxidant activities were found to attenuate the As-induced oxidative stress, testicular damage, and sperm abnormalities via regulating the expressions of Nfe2l2, StAR and Ppargc1a. The study revealed that ellagic and ferulic acids might be potential therapeutic options to protect the male reproductive system from As-poisoning.

摘要

砷(As)引起的氧化应激除了引起全身性影响外,还会导致男性生殖毒性。一些植物化学物质通过其抗氧化特性,可能有助于克服这种毒性作用。本研究旨在阐明选定的植物化学物质鞣花酸和阿魏酸对砷诱导的生殖毒性的保护作用。将 42 只健康雄性瑞士白化病小鼠随机分为六组(每组 n=7)。组 A 作为对照组,而组 B 通过饮用水摄入 200ppm 的 As。组 C 和 D 小鼠分别隔日经口给予 50mg/kg BW 的鞣花酸和阿魏酸。组 E 或 F 接受 50mg 鞣花酸或阿魏酸+200ppm 的 As 四十天。鞣花酸和/或阿魏酸显著减少了睾丸组织中砷、蛋白质羰基化(PC)、脂质过氧化(LPO)的积累,以及改变抗氧化酶(CAT 和 SOD)活性、还原型谷胱甘肽(GSH)和总抗氧化能力(TAC)。植物化学物质处理显著改善了由 As 引起的精子功能(活力、功能膜完整性、Δψ和精子运动学,如总活力、快速、渐进运动和 A 型(STR>80%,ALH>2.5μm)和睾丸损伤(p<0.05)。这些植物化学物质由于其抗氧化活性,通过调节 Nfe2l2、StAR 和 Ppargc1a 的表达,被发现可以减轻砷诱导的氧化应激、睾丸损伤和精子异常。该研究表明,鞣花酸和阿魏酸可能是保护男性生殖系统免受砷中毒的潜在治疗选择。

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