Journal
TOXICOLOGY LETTERS
Volume 366, Issue -, Pages 45-57Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2022.06.010
Keywords
Humidifier disinfectants; Endothelial cells; CMIT/MIT; Oxidative phosphorylation; Mitochondrial dynamics
Categories
Funding
- National Institute of Environmental Research (NIER) - Ministry of Environment (ME) of the Republic of Korea [NIER-2019-04-02-070, NIER-202104-02-055]
Ask authors/readers for more resources
The mixture of CMIT/MIT, commonly used in consumer products, significantly impairs mitochondrial function and dynamics, resulting in endothelial barrier dysfunction, shedding light on the role of mitochondrial damage in CMIT/MIT-associated health effects.
The mixture of 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT, chloromethylisothiazolinone) and 2-methyl-4-isothiazolin-3-one (MIT, methylisothiazolinone) is a commonly used biocide in consumer products. Despite the health issues related to its usage in cosmetics and humidifier disinfectants (HD), understanding its adverse outcome is still limited. Using in vitro cell lines and ex vivo rat models, we examined the effects of CMIT/MIT on the cellular redox homeostasis and energy metabolism in the brain microvascular endothelium, a highly restrictive interface between the bloodstream and brain. In murine bEND.3 and human hCMEC/D3, CMIT/MIT significantly amplified the mitochondrial-derived oxidative stress causing disruption of the mitochondrial membrane potential and oxidative phosphorylation at a sub-lethal concentration (1 mu g/mL) or treatment duration (1 h). In addition, CMIT/MIT significantly increased a dynamic imbalance between mitochondrial fission and fusion, and endogenous pathological stressors significantly potentiated the CMIT/MIT-induced endothelial dysfunction. Notably, in the brain endothelium isolated from intravenously CMIT/MITadministered rats, we observed significant mitochondrial damage and decreased tight junction protein. Taken together, we report that CMIT/MIT significantly impaired mitochondrial function and dynamics resulting in endothelial barrier dysfunction, giving an insight into the role of mitochondrial damage in CMIT/MIT-associated systemic health effects.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available