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噪声和银纳米颗粒通过 CYP450/NF-Kappa B2 和 p53 信号通路诱导大鼠模型的肝毒性。

Noise and silver nanoparticles induce hepatotoxicity via CYP450/NF-Kappa B 2 and p53 signaling pathways in a rat model.

机构信息

Department of Occupational Health Engineering, Faculty of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.

Department of Occupational Health Engineering, Faculty of Public Health, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

Toxicol Ind Health. 2024 Apr;40(4):206-219. doi: 10.1177/07482337241233317. Epub 2024 Feb 15.

DOI:10.1177/07482337241233317
PMID:38358440
Abstract

Co-exposure to noise and nanomaterials, such as silver nanoparticles (Silver-NPs), is a common occurrence in today's industries. This study aimed to investigate the effects of exposure to noise and the administration of silver-NPs on the liver tissue of rats. Thirty-six adult male albino Wistar rats were randomly divided into six groups: a control group (administered saline intraperitoneally), two groups administered different doses of Silver-NPs (50 mg/kg and 100 mg/kg, 5 days a week for 28 days), two groups exposed to noise in addition to Silver-NPs (at the same doses as mentioned before), and a group exposed only to noise (104 dB, 6 hours a day, 5 days a week for 4 weeks). Blood samples were taken to assess hepatic-functional alterations, such as serum ALP, ALT, and AST levels. Additionally, biochemical parameters (MDA, GPX, and CAT) and the silver concentration in the liver were measured. Histopathological analysis, mRNA expression (P53 and NF-κB), protein expression (CYP450), and liver weight changes in rats were also documented. The study found that the administration of Silver-NPs and exposure to noise resulted in elevated levels of ALP, ALT, AST, and MDA ( < .01). Conversely, GPX and CAT levels decreased in all groups compared with the control group ( < .0001). There was a significant increase ( < .05) in liver weight and silver concentration in the liver tissues of groups administered Silver-NPs (50 mg/kg) plus noise exposure, Silver-NPs (100 mg/kg), and Silver-NPs (100 mg/kg) plus noise exposure, respectively. The expression rate of P53, NF-κB, and cytochromes P450 (CYPs-450) was increased in the experimental groups ( < .05). These findings were further confirmed by histopathological changes. In conclusion, this study demonstrated that exposure to noise and the administration of Silver-NPs exacerbated liver damage by increasing protein and gene expression, causing hepatic necrosis, altering biochemical parameters, and affecting liver weight.

摘要

同时接触噪声和纳米材料,如银纳米粒子(Silver-NPs),在当今的工业中很常见。本研究旨在探讨暴露于噪声和给予银纳米粒子对大鼠肝组织的影响。将 36 只成年雄性白化 Wistar 大鼠随机分为六组:对照组(腹腔内给予生理盐水)、两组给予不同剂量的 Silver-NPs(50mg/kg 和 100mg/kg,每周 5 天,共 28 天)、两组在给予 Silver-NPs 的同时暴露于噪声(剂量与前文相同),以及一组仅暴露于噪声(104dB,每天 6 小时,每周 5 天,共 4 周)。采集血样以评估肝功能改变,如血清碱性磷酸酶(ALP)、丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平。此外,还测量了生化参数(MDA、GPX 和 CAT)和肝脏中的银浓度。还记录了大鼠的组织病理学分析、mRNA 表达(P53 和 NF-κB)、蛋白表达(CYP450)和肝重变化。研究发现,给予 Silver-NPs 和暴露于噪声导致 ALP、ALT、AST 和 MDA 水平升高(<.01)。相反,与对照组相比,所有组的 GPX 和 CAT 水平均降低(<.0001)。给予 Silver-NPs(50mg/kg)加噪声暴露、Silver-NPs(100mg/kg)和 Silver-NPs(100mg/kg)加噪声暴露的大鼠肝脏重量和肝脏中银浓度显著增加(<.05)。实验组中 P53、NF-κB 和细胞色素 P450(CYPs-450)的表达率增加(<.05)。这些发现通过组织病理学变化进一步得到证实。总之,本研究表明,暴露于噪声和给予 Silver-NPs 通过增加蛋白质和基因表达加剧了肝损伤,导致肝坏死,改变生化参数,并影响肝重。

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