Intracellular glutathione availability, rather than vitamin C supplementation, determines endothelial cell resistance to water-soluble cigarette smoke toxicants
5 affiliations
- 1Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción
- 2Departamento de Morfología y Función, Facultad de Salud y Ciencias Sociales, Universidad de Las Américas
- 3Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción
- 4Departamento de Fisiología, Facultad de Ciencias Biológicas, Universidad de Concepción
- 5Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello
Abstract
Smoking involves chronic exposure to cigarette smoke toxicants, which is associated with the development of vascular disease characterized by endothelial dysfunction. We examined the role of glutathione and vitamin C in antioxidant defense in endothelial cells exposed to water-soluble cigarette smoke toxicants. Exposure to cigarette smoke-conditioned medium decreased cell viability in a concentration and time-dependent manner, with rapid glutathione depletion and recovery. Cells exposed to non-lethal concentrations recovered their glutathione levels in a manner related with enhanced cell survival, and disruption of glutathione metabolism with L-buthionine-(S,R)-sulfoximine (BSO) drastically decreased cellular resistance to cigarette smoke toxicity and increased cell death. These negative effects were augmented in cells treated with graded hydrogen peroxide concentrations following exposure to cigarette smoke-conditioned medium. Intracellular vitamin C did not provide sustained protection against cigarette smoke toxicity and did not enhance glutathione recovery following oxidative challenge. Moreover, exposure to cigarette smoke-conditioned medium failed to affect the transport of reduced (ascorbic acid) or oxidized (dehydroascorbic acid) vitamin C by endothelial cells, regardless of the status of intracellular glutathione or vitamin C. We conclude that glutathione and vitamin C possess overlapping but clearly distinct functions in the response of cells to oxidative challenge. Specifically, in endothelial cells exposed to soluble cigarette smoke toxicants, glutathione was the major determinant against cigarette smoke toxicity.
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BibTeX
@article{onate2026intracellular,
title = {{Intracellular glutathione availability, rather than vitamin C supplementation, determines endothelial cell resistance to water-soluble cigarette smoke toxicants}},
author = {Gloria Oñate and Perla Salgado and Paula A. Guzmán and Alejandra Muñoz and Catalina Alarcon-Navarro and Solange P. Arriagada and Gustavo Moraga-Cid and Carola Muñoz-Montesino and Marcell Gatica and Coralia I. Rivas},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1924584},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1924584/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Intracellular glutathione availability, rather than vitamin C supplementation, determines endothelial cell resistance to water-soluble cigarette smoke toxicants
AU - Gloria Oñate
AU - Perla Salgado
AU - Paula A. Guzmán
AU - Alejandra Muñoz
AU - Catalina Alarcon-Navarro
AU - Solange P. Arriagada
AU - Gustavo Moraga-Cid
AU - Carola Muñoz-Montesino
AU - Marcell Gatica
AU - Coralia I. Rivas
PY - 2026
DA - 2026/10/28
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1924584
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1924584/full
AB - Smoking involves chronic exposure to cigarette smoke toxicants, which is associated with the development of vascular disease characterized by endothelial dysfunction. We examined the role of glutathione and vitamin C in antioxidant defense in endothelial cells exposed to water-soluble cigarette smoke toxicants. Exposure to cigarette smoke-conditioned medium decreased cell viability in a concentration and time-dependent manner, with rapid glutathione depletion and recovery. Cells exposed to non-lethal concentrations recovered their glutathione levels in a manner related with enhanced cell survival, and disruption of glutathione metabolism with L-buthionine-(S,R)-sulfoximine (BSO) drastically decreased cellular resistance to cigarette smoke toxicity and increased cell death. These negative effects were augmented in cells treated with graded hydrogen peroxide concentrations following exposure to cigarette smoke-conditioned medium. Intracellular vitamin C did not provide sustained protection against cigarette smoke toxicity and did not enhance glutathione recovery following oxidative challenge. Moreover, exposure to cigarette smoke-conditioned medium failed to affect the transport of reduced (ascorbic acid) or oxidized (dehydroascorbic acid) vitamin C by endothelial cells, regardless of the status of intracellular glutathione or vitamin C. We conclude that glutathione and vitamin C possess overlapping but clearly distinct functions in the response of cells to oxidative challenge. Specifically, in endothelial cells exposed to soluble cigarette smoke toxicants, glutathione was the major determinant against cigarette smoke toxicity.
SN - 1663-9812
ER -