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加湿器消毒剂成分聚六亚甲基胍磷酸盐(PHMG-p)暴露对眼干的影响:基于氢核磁共振代谢组学的大鼠模型研究

Effects of Exposure of PHMG-p, a Humidifier Disinfectant Component, on Eye Dryness: A Study on a Rat Model Based on H-NMR Metabolomics.

作者信息

Lee Jung Dae, Kim Hyang Yeon, Oh Soo Bean, Goo Hyeyoon, Cho Kyong Jin, Hwang Gi-Wook, Kim Suhkmann, Kim Kyu-Bong

机构信息

College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea.

Center for Human Risk Assessment, Dankook University, Cheonan 31116, Republic of Korea.

出版信息

Int J Mol Sci. 2025 Sep 5;26(17):8660. doi: 10.3390/ijms26178660.

Abstract

Polyhexamethylene guanidine phosphate (PHMG-p), a widely used disinfectant component in household humidifiers, has been implicated in various health issues, including pulmonary toxicity. Many people use humidifiers to improve dry eye disease (DED). The current study was performed to elucidate the effect of PHMG-p on eye dryness in a rat model using metabolomics. Male Sprague Dawley rats were exposed to PHMG-p (0.1% and 0.3%) following a previously established DED induction model using scopolamine hydrobromide and desiccation stress. Ocular surface damage was assessed using corneal fluorescein staining, tear volume measurement, and tear break-up time (TBUT). Plasma and urine samples were analyzed using H-NMR-based metabolomics to identify metabolic alterations associated with PHMG-P-p exposure and DED pathogenesis. PHMG-p exposure exacerbated DED symptoms, as evidenced by a significant reduction in tear volume, shorter TBUT, and increased corneal damage compared to the control group. Metabolomic profiling identified distinct metabolic changes in PHMG-p-exposed groups, including alterations in glutamate, glycine, citrate, and succinate metabolism. These metabolic changes correlated with increased levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α in the corneal and lacrimal gland tissues. Our findings suggest that PHMG-p exposure contributes to DED pathophysiology by inducing metabolic disturbances and inflammatory responses in the ocular surface. This study highlights the need for further investigation into the potential risks of PHMG-p exposure on ocular health and provides novel insights into the metabolic underpinnings of DED.

摘要

聚六亚甲基胍磷酸盐(PHMG-p)是家用加湿器中广泛使用的一种消毒剂成分,它与包括肺部毒性在内的各种健康问题有关。许多人使用加湿器来改善干眼症(DED)。本研究旨在利用代谢组学阐明PHMG-p对大鼠干眼症模型眼干的影响。雄性Sprague Dawley大鼠在使用氢溴酸东莨菪碱和干燥应激建立的DED诱导模型后,暴露于PHMG-p(0.1%和0.3%)。使用角膜荧光素染色、泪液体积测量和泪膜破裂时间(TBUT)评估眼表损伤。使用基于氢核磁共振的代谢组学分析血浆和尿液样本,以识别与PHMG-p暴露和DED发病机制相关的代谢改变。与对照组相比,PHMG-p暴露加剧了DED症状,表现为泪液体积显著减少、TBUT缩短和角膜损伤增加。代谢组学分析确定了PHMG-p暴露组的明显代谢变化,包括谷氨酸、甘氨酸、柠檬酸和琥珀酸代谢的改变。这些代谢变化与角膜和泪腺组织中白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α等炎症细胞因子水平的升高相关。我们的研究结果表明,PHMG-p暴露通过诱导眼表的代谢紊乱和炎症反应,促进了DED的病理生理过程。本研究强调需要进一步调查PHMG-p暴露对眼部健康的潜在风险,并为DED的代谢基础提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1131/12429713/fe4b1b92b867/ijms-26-08660-g001.jpg

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