Biomol Ther  
Effects of Several Cosmetic Preservatives on ROS-Dependent Apoptosis of Rat Neural Progenitor Cells
Onjeon Ryu1, Bo Kyung Park1, Minji Bang1, Kyu Suk Cho1, Sung Hoon Lee2, Edson Luck T. Gonzales1, Sung Min Yang1, Seonmin Kim1, Pyeong Hwa Eun1, Joo Young Lee3, Kyu-Bong Kim4, Chan Young Shin 1 and Kyoung Ja Kwon1,*
1Department of Neuroscience, School of Medicine and Center for Neuroscience Research, Konkuk University, Seoul 05029,
2College of Pharmacy, Chung-Ang University, Seoul 06974,
3BK21plus Team, College of Pharmacy, The Catholic University of Korea, Bucheon 14662,
4College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea
Tel: +82-2-454-5630, Fax: +82-2030-7899
Received: October 31, 2017; Revised: January 5, 2018; Accepted: January 9, 2018; Published online: February 12, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Benzalkonium chloride, diazolidinyl urea, and imidazolidinyl urea are commonly used preservatives in cosmetics. Recent reports suggested that these compounds may have cellular and systemic toxicity in high concentration. In addition, diazolidinyl urea and imidazolidinyl urea are known formaldehyde (FA) releasers, raising concerns for these cosmetic preservatives. In this study, we investigated the effects of benzalkonium chloride, diazolidinyl urea, and imidazolidinyl urea on ROS-dependent apoptosis of rat neural progenitor cells (NPCs) in vitro. Cells were isolated and cultured from embryonic day 14 rat cortices. Cultured cells were treated with 1-1,000 nM benzalkonium chloride, and 1-50 μM diazolidinyl urea or imidazolidinyl urea at various time points to measure the reactive oxygen species (ROS). PI staining, MTT assay, and live-cell imaging were used for cell viability measurements. Western blot was carried out for cleaved caspase-3 and cleaved caspase-8 as apoptotic protein markers. In rat NPCs, ROS production and cleaved caspase-8 expression were increased while the cell viability was decreased in high concentrations of these substances. These results suggest that several cosmetic preservatives at high concentrations can induce neural toxicity in rat brains through ROS induction and apoptosis.
Keywords: Benzalkonium chloride, Diazolidinyl urea, Imidazolidinyl urea, Apoptosis, Cosmetic preservatives, Reactive oxygen species

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