<br>通过氧化应激机制评估聚（六亚甲基二氰基胍-六亚甲基二胺）盐酸盐诱导的发育神经毒性：神经元细胞和斑马鱼的综合方法,Journal of Hazardous Materials

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通过氧化应激机制评估聚（六亚甲基二氰基胍-六亚甲基二胺）盐酸盐诱导的发育神经毒性：神经元细胞和斑马鱼的综合方法
Journal of Hazardous Materials ( IF 12.2 ) Pub Date : 2023-12-01 , DOI: 10.1016/j.jhazmat.2023.133146
Ha-Na Oh ₁ , Donggon Yoo ₂ , Seungmin Park ₂ , Sangwoo Lee ₂ , Woo-Keun Kim ₂

Affiliation

聚（六亚甲基双氰基胍-六亚甲基二胺）盐酸盐（PHMB）是一种具有广谱抗菌活性的杀菌剂。它在消费品中用作消毒剂和防腐剂会导致人类接触 PHMB。PHMB 的毒性研究主要集中在全身毒性或皮肤刺激性;然而，其对发育神经毒性（DNT）的影响和潜在机制知之甚少。在本研究中，使用 IMR-32 和 SH-SY5Y 细胞系和斑马鱼评估了 PHMB 的 DNT 效应。在两种细胞系中，PHMB 浓度≥ 10 μM 减少了神经突生长，并且在浓度高达 40 μM 时观察到细胞毒性。PHMB 调节神经发育基因的表达并诱导活性氧（ROS）产生和线粒体功能障碍。用 N-乙酰半胱氨酸治疗逆转了 PHMB 的毒性作用。对斑马鱼胚胎的毒性试验表明，PHMB 降低了活力和心率，并导致孵化不规则。1-4 μM 的 PHMB 浓度降低了转基因斑马鱼的大脑和脊髓宽度，并减弱了髓鞘形成过程。此外，PHMB 调节斑马鱼神经发育基因的表达并诱导 ROS 积累。这些结果表明，PHMB 通过 ROS 依赖性机制在体外和体内发挥 DNT 效应，突出了 PHMB 暴露的风险。

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Assessment of poly(hexamethylenebicyanoguanide-hexamethylenediamine) hydrochloride-induced developmental neurotoxicity via oxidative stress mechanism: Integrative approaches with neuronal cells and zebrafish

Poly(hexamethylenebicyanoguanide-hexamethylenediamine) hydrochloride (PHMB) is a biocide with a broad spectrum of antibacterial activity. Its use as a disinfectant and preservative in consumer products results in human exposure to PHMB. Toxicity studies on PHMB mainly focus on systemic toxicity or skin irritation; however, its effects on developmental neurotoxicity (DNT) and the underlying mechanisms are poorly understood. In this study, the DNT effects of PHMB were evaluated using IMR-32 and SH-SY5Y cell lines and zebrafish. In both cell lines, PHMB concentrations ≥ 10 µM reduced neurite outgrowth, and cytotoxicity was observed at concentrations up to 40 µM. PHMB regulated expression of neurodevelopmental genes and induced reactive oxygen species (ROS) production and mitochondrial dysfunction. Treatment with N-acetylcysteine reversed the toxic effects of PHMB. Toxicity tests on zebrafish embryos showed that PHMB reduced viability and heart rate and caused irregular hatching. PHMB concentrations of 1–4 µM reduced the width of the brain and spinal cord of transgenic zebrafish and attenuated myelination processes. Furthermore, PHMB modulated expression of neurodevelopmental genes in zebrafish and induced ROS accumulation. These results suggested that PHMB exerted DNT effects in vitro and in vivo through a ROS-dependent mechanism, highlighting the risk of PHMB exposure.

更新日期：2023-12-01

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