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N-乙酰半胱氨酸联合治疗减轻全氟辛酸诱导的雄性大鼠生殖毒性。

N-acetyl cysteine co-treatment abates perfluorooctanoic acid-induced reproductive toxicity in male rats.

作者信息

Owumi Solomon E, Akomolafe Ayomide P, Imosemi Innocent O, Odunola Oyeronke A, Oyelere Adegboyega K

机构信息

Change-Lab, CRMB Laboratory, Department of Biochemistry, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, Nigeria.

Neuroanatomy Research Laboratories, Department of Anatomy, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, Nigeria.

出版信息

Andrologia. 2021 Jun;53(5):e14037. doi: 10.1111/and.14037. Epub 2021 Mar 16.

DOI:10.1111/and.14037
PMID:33724529
Abstract

Perfluorooctanoic acid is a synthetic perfluoroalkyl-persistent in the environment and toxic to humans. N-acetylcysteine is a pro-drug of both amino acid l-cysteine and glutathione-a non-enzymatic antioxidant. N-acetylcysteine serves as an antidote for paracetamol poisoning and alleviates cellular oxidative and inflammatory stressors. We investigated N-acetylcysteine role against reproductive toxicity in male Wistar rats (weight: 140-220 g; 10 weeks old) posed by perfluorooctanoic acid exposure. Randomised rat cohorts were dosed both with perfluorooctanoic acid (5 mg/kg; p.o) or co-dosed with N-acetylcysteine (25 and 50 mg/kg p.o) for 28 days. Sperm physiognomies, biomarkers of testicular function and reproductive hormones, oxidative stress and inflammation were evaluated. Co-treatment with N-acetylcysteine significantly (p < .05) reversed perfluorooctanoic acid-mediated decreases in reproductive enzyme activities, and adverse effect on testosterone, luteinising and follicle-stimulating hormone concentrations. N-acetylcysteine treatment alone, improved sperm motility, count and viability, and reduced total sperm abnormalities. Co-treatment with N-acetylcysteine mitigated perfluorooctanoic acid-induced alterations in sperm function parameters. N-acetylcysteine abated (p < .05) perfluorooctanoic acid-induced oxidative stress in experimental rats testes and epididymis, and generally improved antioxidant enzyme activities and cellular thiol levels. Furthermore, N-acetylcysteine suppressed inflammatory responses and remedied perfluorooctanoic acid-mediated histological injuries in rat. Cooperatively, N-acetylcysteine enhanced reproductive function in perfluorooctanoic acid dosed rats, by lessening oxidative and nitrative stressors and mitigated inflammatory responses in the examined organ.

摘要

全氟辛酸是一种在环境中持久存在的合成全氟烷基物质,对人类有毒。N-乙酰半胱氨酸是氨基酸L-半胱氨酸和谷胱甘肽(一种非酶抗氧化剂)的前体药物。N-乙酰半胱氨酸可作为对乙酰氨基酚中毒的解毒剂,并减轻细胞氧化和炎症应激源。我们研究了N-乙酰半胱氨酸对全氟辛酸暴露引起的雄性Wistar大鼠(体重:140-220克;10周龄)生殖毒性的作用。将大鼠随机分组,分别给予全氟辛酸(5毫克/千克;口服)或与N-乙酰半胱氨酸(25和50毫克/千克口服)联合给药28天。评估了精子形态、睾丸功能和生殖激素的生物标志物、氧化应激和炎症。与N-乙酰半胱氨酸联合治疗显著(p<0.05)逆转了全氟辛酸介导的生殖酶活性降低,以及对睾酮、黄体生成素和促卵泡激素浓度的不良影响。单独使用N-乙酰半胱氨酸治疗可改善精子活力、数量和存活率,并减少总精子异常。与N-乙酰半胱氨酸联合治疗减轻了全氟辛酸诱导的精子功能参数改变。N-乙酰半胱氨酸减轻了(p<0.05)全氟辛酸诱导的实验大鼠睾丸和附睾中的氧化应激,并总体上提高了抗氧化酶活性和细胞硫醇水平。此外,N-乙酰半胱氨酸抑制了炎症反应,并修复了全氟辛酸介导的大鼠组织学损伤。协同作用下,N-乙酰半胱氨酸通过减轻氧化和硝化应激源以及减轻所检查器官中的炎症反应,增强了全氟辛酸给药大鼠的生殖功能。

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