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甘草对氯化铜诱导的大脑氧化应激的缓解作用:生化、组织病理学、免疫组织化学和遗传毒性研究。

Alleviative effect of licorice on copper chloride-induced oxidative stress in the brain: biochemical, histopathological, immunohistochemical, and genotoxic study.

机构信息

Departments of Forensic Medicine & Clinical Toxicology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Departments of Community, Environmental & Occupational Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

出版信息

Environ Sci Pollut Res Int. 2017 Aug;24(22):18585-18595. doi: 10.1007/s11356-017-9503-6. Epub 2017 Jun 24.

DOI:10.1007/s11356-017-9503-6
PMID:28647874
Abstract

Although copper is an essential micronutrient involved in a variety of biological processes indispensable for sustaining life, it can be toxic when administered in excess. Licorice (Glycyrrhizaglabra) has been used in Chinese folk medicine for the treatment of various disorders. Licorice has the biological capabilities of detoxication, antioxidation, and antiinfection. Here, we test the hypothesis that licorice could ameliorate copper-induced neurotoxic and genotoxic effects in adult male albino rats. For this purpose, 48 adult male albino rats were randomized into five groups: group I (8 rats), untreated control; group II (16 rats), subdivided into; vehicle control IIa (8 rats) which received 1 mL saline twice weekly intraperitoneally for 8 weeks and vehicle control IIb (8 rats) received 0.5 mL distilled water/day orally gavaged for 8 weeks; group III (8 rats), treated with licorice dissolved in 0.5 mL of distilled water, 50 mg/kg b.w./day orally gavaged for 8 weeks; group IV (8 rats), copper chloride (CuCl) dissolved in 0.5 mL saline, 7 mg/kg b.w. twice weekly intraperitoneal for 8 weeks; and group V (8 rats), CuCl + licorice (the same previously mentioned doses) licorice extract were orally given for 10 days before treatment was initiated then followed by CuCl intraperitoneally for 8 weeks. We found that CuCl exposure significantly increased brain oxidative stress as manifested by elevated malondialdehyde levels, decreased reduced glutathione content, and depressed antioxidant enzyme activities in brain tissues when compared with control groups. This was accompanied by histopathological changes in the form of increased cellularity and swelling of astrocytes that showed dense eosinophilic cytoplasm, pyknotic nuclei, and multiple apoptotic bodies that associated with degenerated neurons with deep eosinophilic cytoplasm. Also, strong Bax immunoreactions in the brain were detected. Furthermore, comet assay results confirmed CuCl-related oxidative DNA damage. Notably, all these changes were partially ameliorated in rats treated concomitantly with licorice and CuCl. Our results showed that licorice exerts protective effects against CuCl-induced neuro- and genotoxicities. These effects may be attributed to the antioxidative property of licorice.

摘要

尽管铜是一种必需的微量元素,参与了许多对维持生命至关重要的生物过程,但当过量摄入时,它也可能有毒。甘草(Glycyrrhizaglabra)已在中国民间医学中用于治疗各种疾病。甘草具有解毒、抗氧化和抗感染的生物学能力。在这里,我们检验了甘草可以改善成年雄性白化大鼠铜诱导的神经毒性和遗传毒性的假设。为此,将 48 只成年雄性白化大鼠随机分为五组:I 组(8 只大鼠),未处理对照组;II 组(16 只大鼠),分为以下两组:vehicle control IIa(8 只大鼠),每周两次腹腔注射 1mL 生理盐水,共 8 周;vehicle control IIb(8 只大鼠),每天口服 0.5mL 蒸馏水,共 8 周;III 组(8 只大鼠),甘草溶于 0.5mL 蒸馏水,50mg/kg b.w./天,口服灌胃 8 周;IV 组(8 只大鼠),铜氯(CuCl)溶于 0.5mL 生理盐水,7mg/kg b.w.每周两次腹腔注射,共 8 周;V 组(8 只大鼠),CuCl+甘草(剂量同上),先口服给药 10 天,然后开始 CuCl 腹腔注射 8 周。我们发现,与对照组相比,CuCl 暴露显著增加了大脑的氧化应激,表现为丙二醛水平升高、还原型谷胱甘肽含量降低和大脑组织抗氧化酶活性降低。这伴随着星形胶质细胞的细胞数量增加和肿胀的组织病理学变化,星形胶质细胞表现出浓密的嗜酸性细胞质、固缩核和多个凋亡小体,以及与深嗜酸性细胞质的退行性神经元相关的凋亡小体。此外,在大脑中检测到强烈的 Bax 免疫反应。此外,彗星试验结果证实了 CuCl 相关的氧化 DNA 损伤。值得注意的是,在同时给予甘草和 CuCl 的大鼠中,这些变化部分得到了改善。我们的结果表明,甘草对 CuCl 诱导的神经毒性和遗传毒性具有保护作用。这些作用可能归因于甘草的抗氧化特性。

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