Effects of Several Cosmetic Preservatives on ROS-Dependent Apoptosis of Rat Neural Progenitor Cells

Abstract

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.

The Beast of Beauty: Environmental and Health Concerns of Toxic Components in Cosmetics

“…The results showed that cellular viability and count severely decreased after 24 h of treatment with imidazolidinyl or diazolidinyl urea and ROS production and apoptosis significantly increased. These results also showed that imidazolidinyl urea and diazolidinyl urea induce oxidative stress in mitochondria [74]. However, there is still ambiguity because these compounds can also be involved in cell death followed by autophagy.…”

“…Experimental results of a study conducted to analyze the effects of BAC in a dose-dependent manner showed neurites concentration decrease in corneal nerves and also induction of oxidative stress that leads to cholinergic neurotoxicity [73]. Recently, a study showed that the overproduction of ROS results in the destruction of caspase-8 expression, a result, the cell viability waned, when rat neural progenitor cells (NPCs) were exposed to a higher concentration of BAC [74]. Previous data have shown that cosmetic products with a high concentration of BAC have high potency to induce the severe ROS-mediated neurotoxicity in rats that leads to apoptosis in later stages.…”

“…Upon the hydrolysis of diazolidinyl urea, formaldehyde is released that may cause itching, skin redness, and irritation. Ryu et al [74] reported different types of cosmetic preservatives such as diazolidinyl urea, benzalkonium chloride, and imidazolidinyl on rat NPCs cell culture. In this study, they assessed the ROS released by treated cells at different concentrations of 1-50 µM diazolidinyl urea or imidazolidinyl urea and 1-1000 nM benzalkonium chloride at different time laps.…”

Inhaled Kathon may induce eosinophilia‐mediated disease in the lung

“…Similarly, methylisothiazolinone (MIT) and formaldehyde have been suggested to be among the main causes of contact allergy caused in workers . Several cosmetic preservatives such as benzalkonium chloride, diazolinidyl urea, and imidazolinidyl urea also induced apoptotic cell death by increasing the generation of oxygen‐mediated free radicals in neural progenitor cells . Notably, since 1995, patients with idiopathic pulmonary fibrosis occurred in South Korea, including mainly infants and pregnant women, and among these patients, about 58% of children died .…”

Cosmetics’ Safety: Gray Areas with Darker Inside

“…Diazolidinyl urea and imidazolidinyl urea are known formaldehyde releasers. The data from FDA showed that 20% cosmetic products are formaldehyde-releasers and among them, imidazolidinyl urea is the most widely used [28] . Chronic exposure to benzalkonium chloride has deleterious effects via oxidative stress, leading to cholinergic neurotoxicity [29] .…”