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A Commonly Used Biocide 2-N-octyl-4-isothiazolin-3-oneInduces Blood–Brain Barrier Dysfunction via Cellular Thiol Modification and Mitochondrial Damage
- Source :
- International Journal of Molecular Sciences, Volume 22, Issue 5, International Journal of Molecular Sciences, Vol 22, Iss 2563, p 2563 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI, 2021.
-
Abstract
- Isothiazolinone (IT) biocides are potent antibacterial substances commonly used as preservatives or disinfectants, and 2-n-Octyl-4-isothiazolin-3-one (OIT<br />octhilinone) is a common IT biocide that is present in leather products, glue, paints, and cleaning products. Although humans are exposed to OIT through personal and industrial use, the potentially deleterious effects of OIT on human health are still unknown. To investigate the effects of OIT on the vascular system, which is continuously exposed to xenobiotics through systemic circulation, we treated brain endothelial cells with OIT. OIT treatment significantly activated caspase-3-mediated apoptosis and reduced the bioenergetic function of mitochondria in a bEnd.3 cell-based in vitro blood–brain barrier (BBB) model. Interestingly, OIT significantly altered the thiol redox status, as evidenced by reduced glutathione levels and protein S-nitrosylation. The endothelial barrier function of bEnd.3 cells was significantly impaired by OIT treatment. OIT affected mitochondrial dynamics through mitophagy and altered mitochondrial morphology in bEnd.3 cells. N-acetyl cysteine significantly reversed the effects of OIT on the metabolic capacity and endothelial function of bEnd.3 cells. Taken together, we demonstrated that the alteration of the thiol redox status and mitochondrial damage contributed to OIT-induced BBB dysfunction, and we hope that our findings will improve our understanding of the potential hazardous health effects of IT biocides.
- Subjects :
- 0301 basic medicine
Mitochondrion
Pharmacology
medicine.disease_cause
Antioxidants
lcsh:Chemistry
chemistry.chemical_compound
Mice
0302 clinical medicine
Mitophagy
oxidative stress
lcsh:QH301-705.5
Spectroscopy
Membrane Potential, Mitochondrial
Cell Death
Brain
General Medicine
Computer Science Applications
Mitochondria
medicine.anatomical_structure
Blood-Brain Barrier
Blood–brain barrier
Catalysis
Article
Cell Line
Inorganic Chemistry
Isothiazolinone
03 medical and health sciences
protein S-nitrosylation (SNO)
mitochondrial dysfunction
medicine
Animals
Humans
Sulfhydryl Compounds
Physical and Theoretical Chemistry
Molecular Biology
isothiazolinone (IT) biocide
Tight Junction Proteins
Organic Chemistry
Endothelial Cells
Glutathione
2-n-Octyl-4-isothiazolin-3-one (OIT)
Acetylcysteine
Thiazoles
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
chemistry
Apoptosis
blood–brain barrier (BBB) model
Proteolysis
Energy Metabolism
Reactive Oxygen Species
030217 neurology & neurosurgery
Oxidative stress
Cysteine
Disinfectants
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 22
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....49cc60cfde354c0324f55eea940b1a85