Methylisothiazolinone induces apoptotic cell death via matrix metalloproteinase activation in human bronchial epithelial cells

Park, Eun-Jung; Seong, Eunsol

doi:10.1016/j.tiv.2019.104661

Cited by 14 publications

(10 citation statements)

References 56 publications

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“…More recently, another group demonstrated that MI was capable of inducing cellular death and the activation of pro-inflammatory responses in bronchial epithelial cells (BEAS-2B cells). Additionally, the authors also signaled the possible carcinogenic effect of MI after gene profile analysis [55].…”

Section: Methodsmentioning

confidence: 99%

Isothiazolinone Biocides: Chemistry, Biological, and Toxicity Profiles

et al. 2020

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The importance of isothiazole and of compounds containing the isothiazole nucleus has been growing over the last few years. Isothiazolinones are used in cosmetic and as chemical additives for occupational and industrial usage due to their bacteriostatic and fungiostatic activity. Despite their effectiveness as biocides, isothiazolinones are strong sensitizers, producing skin irritations and allergies and may pose ecotoxicological hazards. Therefore, their use is restricted by EU legislation. Considering the relevance and importance of isothiazolinone biocides, the present review describes the state-of-the-art knowledge regarding their synthesis, antibacterial components, toxicity (including structure–activity–toxicity relationships) outlines, and (photo)chemical stability. Due to the increasing prevalence and impact of isothiazolinones in consumer’s health, analytical methods for the identification and determination of this type of biocides were also discussed.

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Section: Methodsmentioning

confidence: 99%

Isothiazolinone Biocides: Chemistry, Biological, and Toxicity Profiles

et al. 2020

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“…Forty-eight published studies using non-human animal subjects or in vitro toxicology studies were included in the review ( Table 3 ). 16 39 40 41 42 43 44 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 To investigate the hazardous effects of humidifier disinfectants, in vitro studies were performed using various cell lines, and toxicity tests were performed using several animal models. Cytotoxicity, lung fibrosis, and pulmonary genotoxicity due to PHMG exposure were described as a consequence of toxicity testing undertaken shortly after HDLI was reported.…”

Section: Resultsmentioning

confidence: 99%

“… 73 Changes in multiple pathways such as matrix metalloproteinase activation and DNA damage were observed in human bronchial epithelial cells exposed to CMIT/MIT, raising concerns about carcinogenicity. 74 In addition, the mechanism of eosinophil-mediated illness induction was reported. 75 …”

Section: Discussionmentioning

confidence: 99%

Health Effects Associated With Humidifier Disinfectant Use: A Systematic Review for Exploration

et al. 2022

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Background It has been 10 years since the outbreak of lung disease caused by humidifier disinfectants in Korea, but the health effects have not yet been summarized. Therefore, this study aims to systematically examine the health effects of humidifier disinfectants that have been discovered so far. Methods All literature with humidifier disinfectants and their representative components as the main words were collected based on the web, including PubMed, Research Information Sharing Service, and government publication reports. A total of 902 studies were searched, of which 196 were selected. They were divided into four groups: published human studies (group 1), published animal and cytotoxicology studies (group 2), technical reports (group 3), and gray literature (group 4). Results Out of the 196 studies, 97 (49.5%) were published in peer-reviewed journals as original research. Group 1 consisted of 49 articles (50.5%), while group 2 consisted of 48 articles (49.5%). Overall, respiratory diseases such as humidifier disinfectant associated lung injury, interstitial lung disease, and asthma have a clear correlation, but other effects such as liver, heart, thymus, thyroid, fetal growth, metabolic abnormalities, and eyes are observed in toxicological experimental studies, but have not yet been identified in epidemiologic studies. Conclusion The current level of evidence does not completely rule out the effects of humidifier disinfectants on extrapulmonary disease. Based on the toxicological evidence so far, it is required to monitor the population of humidifier disinfectant exposure continuously to see if similar damage occurs.

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“…Furthermore, DDAC was one of the ingredients in humidifier disinfectants that caused idiopathic lung diseases in Korea since 2006. In our previous studies using humidifier disinfectant ingredients such as PHMG-phosphate, MIT, and Kathon, we emphasized the impact of the critical micelle concentration (CMC) on cell death induced by detergents that have amphiphilic activity ( Park et al, 2018 ; Park et al, 2020 ; Park and Seong, 2020 ). In this study, we again demonstrated that cell viability dramatically decrease at a concentration of 4 μg/mL and that there was no significant change in cell viability at higher concentrations.…”

Section: Discussionmentioning

confidence: 99%

Formation of lamellar body-like structure may be an initiator of didecyldimethylammonium chloride-induced toxic response

Park

Seong

Kang

et al. 2020

Toxicology and Applied Pharmacology

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Due to the pandemic of coronavirus disease 2019, the use of disinfectants is rapidly increasing worldwide. Didecyldimethylammonium chloride (DDAC) is an EPA-registered disinfectant, it was also a component in humidifier disinfectants that had caused idiopathic pulmonary diseases in Korea. In this study, we identified the possible pulmonary toxic response and mechanism using human bronchial epithelial (BEAS-2B) cells and mice. First, cell viability decreased sharply at a 4 μg/mL of concentration. The volume of intracellular organelles and the ROS level reduced, leading to the formation of apoptotic bodies and an increase of the LDH release. Secretion of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and matrix metalloproteinase-1 also significantly increased. More importantly, lamellar body-like structures were formed in both the cells and mice exposed to DDAC, and the expression of both the indicator proteins for lamellar body (ABCA3 and Rab11a) and surfactant proteins (A, B, and D) was clearly enhanced. In addition, chronic fibrotic pulmonary lesions were notably observed in mice instilled twice (weekly) with DDAC (500 μg), ultimately resulting in death. Taken together, we suggest that disruption of pulmonary surfactant homeostasis may contribute to DDAC-induced cell death and subsequent pathophysiology and that the formation of lamellar body-like structures may play a role as the trigger. In addition, we propose that the cause of sudden death of mice exposed to DDAC should be clearly elucidated for the safe application of DDAC.

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Methylisothiazolinone induces apoptotic cell death via matrix metalloproteinase activation in human bronchial epithelial cells

Cited by 14 publications

References 56 publications

Isothiazolinone Biocides: Chemistry, Biological, and Toxicity Profiles

Isothiazolinone Biocides: Chemistry, Biological, and Toxicity Profiles

Health Effects Associated With Humidifier Disinfectant Use: A Systematic Review for Exploration

Formation of lamellar body-like structure may be an initiator of didecyldimethylammonium chloride-induced toxic response

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