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地毯灰尘对大鼠肺生化指标及组织学结构的毒性作用:细胞色素P450 2E1及细胞外信号调节激酶/丝裂原活化蛋白激酶信号通路的潜在作用

Toxic effect of carpet dust on the biochemical indices and histological structure of the lung in rats: the potential role of cytochrome P450 2E1 and extracellular signal-regulated kinase/mitogen-activated protein kinase pathways.

作者信息

Salama Abeer, Elgohary Rania, Mowaad Noha, Sadek Doaa, Abdelhamid Walaa

机构信息

Pharmacology Department, National Research Centre, Cairo, Egypt.

Narcotics, Ergogenics and Poisons Department, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt.

出版信息

Biomarkers. 2023 May;28(3):289-301. doi: 10.1080/1354750X.2023.2164905. Epub 2023 Jan 12.

DOI:10.1080/1354750X.2023.2164905
PMID:36588463
Abstract

Carpet dust exposure in the carpet industry causes various respiratory hazards that lead to permanent loss of lung function. This study investigated the potentially toxic effects of knotted and tufted carpet dust on rat lungs and the possible involvement of cytochrome P450 2E1 (CYP2E1) and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathways in the induced toxicity, as well as histological changes in the lung induced by carpet dust. This study divided 48 adult rats into six groups: group I was the control group, group II (vehicle group) received phosphate buffer saline (50 µL/rat), groups III and IV received knotted dust (2.5 and 5 mg/kg, respectively), and groups V and VI received tufted dust (2.5 and 5 mg/kg, respectively). All treatments were intranasally administered once a day for 7 days. Both dust types significantly decreased the lung content of GSH compared with the control. Significantly elevated malondialdehyde (MDA) and nitric oxide (NO) lung contents were observed with an increased CYP2E1, interleukin (IL)-6, nuclear factor kappa B (NF-κβ), and ERK/MAPK. The histological lung structure was moderately affected with a moderately increased number of CD68-positive macrophages in the lung parenchyma of knotted dust-exposed rats, whereas tufted dust exposure severely affected the lung tissue with significantly increased CD68-positive macrophages. Carpet dust exposure could induce oxidative stress and inflammatory response in the lung tissue induction of CYP2E1 that stimulates ERK/MAPK signalling pathway proteins, resulting in elevated MDA, NO and IL-6 levels in the lung tissue with suppressed GSH content. Tufted dust could possess a more toxic response than knotted ones.

摘要

地毯行业中接触地毯灰尘会导致各种呼吸道危害,进而导致肺功能永久性丧失。本研究调查了打结地毯灰尘和簇绒地毯灰尘对大鼠肺部的潜在毒性作用,以及细胞色素P450 2E1(CYP2E1)和细胞外信号调节激酶/丝裂原活化蛋白激酶(ERK/MAPK)通路在诱导毒性中的可能作用,以及地毯灰尘诱导的肺部组织学变化。本研究将48只成年大鼠分为六组:第一组为对照组,第二组(溶剂组)接受磷酸盐缓冲盐水(50 μL/只大鼠),第三组和第四组分别接受打结灰尘(2.5和5 mg/kg),第五组和第六组分别接受簇绒灰尘(2.5和5 mg/kg)。所有处理均通过鼻腔给药,每天一次,持续7天。与对照组相比,两种灰尘类型均显著降低了肺组织中谷胱甘肽(GSH)的含量。随着CYP2E1、白细胞介素(IL)-6、核因子κB(NF-κβ)和ERK/MAPK的增加,丙二醛(MDA)和一氧化氮(NO)的肺组织含量显著升高。肺部组织学结构受到中度影响,在接触打结灰尘的大鼠肺实质中,CD68阳性巨噬细胞数量中度增加,而接触簇绒灰尘则严重影响肺组织,CD68阳性巨噬细胞显著增加。接触地毯灰尘可诱导肺组织中的氧化应激和炎症反应,诱导CYP2E1刺激ERK/MAPK信号通路蛋白,导致肺组织中MDA、NO和IL-6水平升高,同时GSH含量受到抑制。簇绒灰尘可能比打结灰尘具有更强的毒性反应。

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