Mitani Tsuyoshi, Elmarhomy Ahmed Ibrahim Elhossany, Dulamjav Luvsandorj, Anu Enkhtumur, Saitoh Shohei, Ishida Shiro, Oyama Yasuo
Faculty of Integrated Arts and Sciences, Tokushima University, Tokushima 770-8502, Japan.
Graduate School of Integrated Arts and Sciences, Tokushima University, Tokushima 770-8502, Japan.
Chem Biol Interact. 2017 Apr 25;268:31-36. doi: 10.1016/j.cbi.2017.02.017. Epub 2017 Feb 28.
Benzalkonium chloride (BZK) is a common preservative used in pharmaceutical and personal care products. ZnCl was recently reported to significantly potentiate the cytotoxicity of some biocidal compounds. In the present study, therefore, we compared the cytotoxic potency of BZK and then further studied the Zn-related actions of the most cytotoxic agent among BZK, using flow cytometric techniques with appropriate fluorescent probes in rat thymocytes. Cytotoxicity of benzylcetyldimethylammonium (BZK-C16) was more potent that those of benzyldodecyldimethylammonium and benzyldimethyltetradecylammonium. ZnCl (1-10 μM) significantly potentiated the cytotoxicity of BZK-C16 at a sublethal concentration (1 μM). The co-treatment of cells with 3 μM ZnCl and 1 μM BZK-C16 increased the population of both living cells with phosphatidylserine exposed on membrane surfaces and dead cells. BZK-C16 at 0.3-1.0 μM elevated intracellular Zn levels by increasing Zn influx, and augmented the cytotoxicity of 100 μM HO. Zn is concluded to facilitate the toxicity of BZK. We suggest that the toxicity of BZK is determined after taking extracellular (plasma) and/or environmental Zn levels into account.
苯扎氯铵（BZK）是一种用于药品和个人护理产品的常见防腐剂。最近有报道称，氯化锌（ZnCl）能显著增强某些杀菌化合物的细胞毒性。因此，在本研究中，我们比较了BZK的细胞毒性，并使用合适的荧光探针通过流式细胞术进一步研究了大鼠胸腺细胞中BZK中细胞毒性最强的试剂与锌相关的作用。苄基十六烷基二甲基氯化铵（BZK-C16）的细胞毒性比苄基十二烷基二甲基氯化铵和苄基二甲基十四烷基氯化铵更强。在亚致死浓度（1 μM）下，氯化锌（1-10 μM）显著增强了BZK-C16的细胞毒性。用3 μM氯化锌和1 μM BZK-C16共同处理细胞，增加了膜表面暴露有磷脂酰丝氨酸的活细胞和死细胞的数量。0.3-1.0 μM的BZK-C16通过增加锌内流提高了细胞内锌水平，并增强了100 μM H₂O₂的细胞毒性。得出锌会促进BZK毒性的结论。我们建议在考虑细胞外（血浆）和/或环境锌水平后确定BZK的毒性。
