Glutathione is a potential therapeutic target for acrolein toxicity in the cornea.
Acrolein
/ toxicity
Caspase 3
/ genetics
Caspase 7
/ genetics
Cell Survival
/ drug effects
Cells, Cultured
Cornea
/ cytology
Cytoprotection
/ drug effects
Fibroblasts
/ drug effects
Gene Expression Regulation
/ drug effects
Glutathione
/ metabolism
Humans
Lipid Peroxidation
Lipids
/ chemistry
Membrane Potential, Mitochondrial
/ drug effects
Oxidative Stress
Reactive Oxygen Species
Acrolein
Glutathione (GSH)
Human corneal fibroblasts (hCSFs)
Lipid peroxide (LPO)
N-acetyl cysteine (NAC)
Reactive oxygen species (ROS)
Journal
Toxicology letters
ISSN: 1879-3169
Titre abrégé: Toxicol Lett
Pays: Netherlands
ID NLM: 7709027
Informations de publication
Date de publication:
01 Apr 2021
01 Apr 2021
Historique:
received:
01
11
2020
revised:
27
12
2020
accepted:
04
01
2021
pubmed:
10
1
2021
medline:
23
2
2021
entrez:
9
1
2021
Statut:
ppublish
Résumé
Toxic and volatile chemicals are widely used in household products and previously used as warfare agents, causing a public health threat worldwide. This study aimed to evaluate the extent of injury and mechanisms of acrolein toxicity in the cornea. Primary human corneal stromal fibroblasts cultures (hCSFs) from human donor cornea were cultured and exposed to acrolein toxicity with -/+ N-acetylcysteine (NAC) to study the mode of action in the presence of Buthionine sulphoximine (BSO). PrestoBlue and MTT assays were used to optimize acrolein, NAC, and BSO doses for hCSFs. Cell-based assays and qRT-PCR analyses were performed to understand the acrolein toxicity and mechanisms. Acrolein exposure leads to an increased reactive oxygen species (ROS), compromised glutathione (GSH) levels, and mitochondrial dysfunction. The TUNEL and caspase assays showed that acrolein caused cell death in hCSFs. These deleterious effects can be mitigated using NAC in hCSFs, suggesting that GSH can be a potential target for acrolein toxicity in the cornea.
Identifiants
pubmed: 33421550
pii: S0378-4274(21)00006-0
doi: 10.1016/j.toxlet.2021.01.005
pmc: PMC9206442
mid: NIHMS1814122
pii:
doi:
Substances chimiques
Lipids
0
Reactive Oxygen Species
0
Acrolein
7864XYD3JJ
Caspase 3
EC 3.4.22.-
Caspase 7
EC 3.4.22.-
Glutathione
GAN16C9B8O
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
33-42Subventions
Organisme : NEI NIH HHS
ID : R01 EY030774
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY030233
Pays : United States
Organisme : BLRD VA
ID : IK6 BX005646
Pays : United States
Organisme : BLRD VA
ID : I01 BX000357
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY029795
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY017294
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY030234
Pays : United States
Informations de copyright
Copyright © 2021. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors report no declarations of interest.
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