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铜通过调节氧化应激、细胞凋亡、DNA 损伤和炎症诱导脾脏损伤。

Copper Induces Spleen Damage Through Modulation of Oxidative Stress, Apoptosis, DNA Damage, and Inflammation.

机构信息

College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China.

Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, China.

出版信息

Biol Trace Elem Res. 2022 Feb;200(2):669-677. doi: 10.1007/s12011-021-02672-8. Epub 2021 Mar 19.

DOI:10.1007/s12011-021-02672-8
PMID:33740180
Abstract

Copper (Cu) is an essential micronutrient for both humans and animals; however, excessive intake of Cu can be immunotoxic. There are limited studies on spleen toxicity induced by Cu. This study was conducted to investigate the effects of Cu on spleen oxidative stress, apoptosis, and inflammatory responses in mice orally administered with 0 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg of CuSO for 42 days. As discovered in this work, copper sulfate (CuSO) reduced the activities of antioxidant enzymes (SOD, CAT, and GSH-Px), decreased GSH contents, and increased MDA contents. Meanwhile, CuSO induced apoptosis by increasing TUNEL-positive cells in the spleen. Also, CuSO increased the expression of γ-H2AX, which is the marker of DNA damage. Concurrently, CuSO caused inflammation by increasing the mRNA levels of interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). In conclusion, the abovementioned findings demonstrate that over 10 mg/kg CuSO can cause oxidative stress, apoptosis, DNA damage, and inflammatory responses, which contribute to spleen dysfunction in mice.

摘要

铜(Cu)是人类和动物必需的微量元素;然而,摄入过量的铜可能具有免疫毒性。目前关于铜引起的脾脏毒性的研究还很有限。本研究旨在探讨硫酸铜(CuSO)对连续灌胃 42 天的 0mg/kg、10mg/kg、20mg/kg 和 40mg/kg 铜的小鼠脾脏氧化应激、细胞凋亡和炎症反应的影响。结果发现,硫酸铜(CuSO)降低了抗氧化酶(SOD、CAT 和 GSH-Px)的活性,降低了 GSH 含量,增加了 MDA 含量。同时,CuSO 通过增加脾脏中 TUNEL 阳性细胞诱导细胞凋亡。此外,CuSO 通过增加白细胞介素-1β(IL-1β)、IL-2、IL-4、IL-6、IL-12、肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)的 mRNA 水平引起炎症。综上所述,这些发现表明,超过 10mg/kg 的 CuSO 可导致氧化应激、细胞凋亡、DNA 损伤和炎症反应,从而导致小鼠脾脏功能障碍。

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