Glutathione is a potential therapeutic target for acrolein toxicity in the cornea. Toxicol Lett 2021 Apr 01;340:33-42
Date
01/10/2021Pubmed ID
33421550Pubmed Central ID
PMC9206442DOI
10.1016/j.toxlet.2021.01.005Scopus ID
2-s2.0-85099361849 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
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.
Author List
Gupta S, Kamil S, Sinha PR, Rodier JT, Chaurasia SS, Mohan RRAuthor
Shyam S. Chaurasia PhD Associate Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcroleinCaspase 3
Caspase 7
Cell Survival
Cells, Cultured
Cornea
Cytoprotection
Fibroblasts
Gene Expression Regulation
Glutathione
Humans
Lipid Peroxidation
Lipids
Membrane Potential, Mitochondrial
Oxidative Stress
Reactive Oxygen Species