Soybean Extract Ameliorates Lung Injury induced by Uranium Inhalation: An integrated strategy of network pharmacology, metabolomics, and transcriptomics

被引:1
作者
Yang, Xin [1 ]
Liang, Hongying [1 ]
Tang, Yufu [1 ]
Dong, Ruifeng [1 ]
Liu, Qimiao [2 ]
Pang, Wanqing [2 ]
Su, Lixia [1 ]
Gu, Xiaona [1 ]
Liu, Mengya [1 ]
Wu, Qingdong [1 ]
Xue, Xiangming [1 ]
Zhan, Jingming [1 ]
机构
[1] China Inst Radiat Protect, Div Radiol & Environm Med, Taiyuan 030006, Peoples R China
[2] Shanxi Univ, Inst Biomed Sci, Taiyuan 030006, Peoples R China
关键词
Soybean extract; Uranium-induced lung injury; Network pharmacology; Transcriptomics; Metabolomics; DEPLETED URANIUM; CHRONIC INGESTION; GENE-EXPRESSION; TOXICITY; DETOXIFICATION; ACTIVATION; STRESS; CELLS;
D O I
10.1016/j.biopha.2024.117451
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Aim: This study aimed to evaluate the protective effect of soybean extract (SE) against uranium-induced lung injury in rats. Materials and methods: A rat lung injury model was established through nebulized inhalation of uranyl nitrate. Pretreatment with SE or sterile water (control group) by gavage for seven days before uranium exposure and until the experiment endpoints. The levels of uranium in lung tissues were detected by ICP-MS. Paraffin embedding-based hematoxylin & eosin staining and Masson's staining for the lung tissue were performed to observe the histopathological imaging features. A public database was utilized to analyze the network pharmacological association between SE and lung injury. The expression levels of proteins indicating fibrosis were measured by enzyme-linked immunosorbent assay. RNA-seq transcriptomic and LC-MS/MS targeted metabolomics were conducted in lung tissues. Results: Uranium levels in the lung tissues were lower in SE-pretreated rats than in the uranium-treated group. Inflammatory cell infiltration and the deposition of extracellular matrix were attenuated, and the levels of alpha-smooth muscle actin, transforming growth factor beta1, and hydroxyproline decreased in SE-pretreated rats compared to the uranium-treated group. Active ingredients of SE were related to inflammation, oxidative stress, and drug metabolism. A total of 67 differentially expressed genes and 39 differential metabolites were identified in the SE-pretreated group compared to the uranium-treated group, focusing on the drug metabolism-cytochrome P450, glutathione metabolism, IL-17 signaling pathway, complement, and coagulation cascades. Conclusions: These findings suggest that SE may ameliorate uranium-induced pulmonary inflammation and fibrosis by regulating glutathione metabolism, chronic inflammation, and immune regulation.
引用
收藏
页数:13
相关论文
共 62 条
[1]   Potential therapeutic interventions of plant-derived isoflavones against acute lung injury [J].
Aboushanab, Saied A. ;
El-Far, Ali H. ;
Narala, Venkata Ramireddy ;
Ragab, Rokia F. ;
Kovaleva, Elena G. .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2021, 101
[2]   Effect of long-term human exposure to environmental heavy metals on the expression of detoxification and DNA repair genes [J].
Al Bakheet, Saleh A. ;
Attafi, Ibraheem M. ;
Maayah, Zaid H. ;
Abd-Allah, Adel R. ;
Asiri, Yousif A. ;
Korashy, Hesham M. .
ENVIRONMENTAL POLLUTION, 2013, 181 :226-232
[3]   Protocatechuic acid methyl ester modulates fluoride induced pulmonary toxicity in rats [J].
Ameeramja, Jaishabanu ;
Kanagaraj, Vishnu Vignesh ;
Perumal, Ekambaram .
FOOD AND CHEMICAL TOXICOLOGY, 2018, 118 :235-244
[4]   SIMPLE METHOD OF ESTIMATING SEVERITY OF PULMONARY FIBROSIS ON A NUMERICAL SCALE [J].
ASHCROFT, T ;
SIMPSON, JM ;
TIMBRELL, V .
JOURNAL OF CLINICAL PATHOLOGY, 1988, 41 (04) :467-470
[5]  
[ ATSDR ] Agency for Toxic Substances and Disease Registry,, 2013, TOXICOLOGICAL PROFIL
[6]   The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells [J].
Attafi, Ibraheem M. ;
Bakheet, Saleh A. ;
Korashy, Hesham M. .
TOXICOLOGY MECHANISMS AND METHODS, 2020, 30 (03) :197-207
[7]   Herbal decoction Divya-Swasari-Kwath attenuates airway inflammation and remodeling through Nrf-2 mediated antioxidant lung defence in mouse model of allergic asthma [J].
Balkrishna, Acharya ;
Solleti, Siva Kumar ;
Singh, Hoshiyar ;
Verma, Sudeep ;
Sharma, Niti ;
Nain, Pradeep ;
Varshney, Anurag .
PHYTOMEDICINE, 2020, 78
[8]   Nuclear Fuel in a Reactor Accident [J].
Burns, Peter C. ;
Ewing, Rodney C. ;
Navrotsky, Alexandra .
SCIENCE, 2012, 335 (6073) :1184-1188
[9]  
Chen M.L., 2023, Environ. Toxicol, DOI [10.1002/tox.24086, DOI 10.1002/TOX.24086, DOI 10.1002/TOX.24086.61J]
[10]   Stimulation of airway mucin gene expression by interleukin (IL)-17 through IL-6 paracrine/autocrine loop [J].
Chen, Y ;
Thai, P ;
Zhao, YH ;
Ho, YS ;
DeSouza, MM ;
Wu, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (19) :17036-17043