Glutathione Supplementation Attenuates Lipopolysaccharide-induced Mitochondrial Dysfunction and Apoptosis in a Mouse Model of Acute Lung Injury

Acute lung injury (ALI) is a life threatening condition associated with hypoxemia, diffuse alveolar damage, inflammation, and loss of lung function. Lipopolysaccharide (LPS; endotoxin) from the outer membrane of gram-negative bacteria is a major virulence factor involved in the development of ALI. T...

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Main Authors: Saurabh eAggarwal, Christiana eDimitropoulou, Qing eLu, Stephen M Black, Shruti eSharma
Format: Article
Language:English
Published: Frontiers Media S.A. 2012-05-01
Series:Frontiers in Physiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00161/full
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author Saurabh eAggarwal
Christiana eDimitropoulou
Qing eLu
Stephen M Black
Shruti eSharma
author_facet Saurabh eAggarwal
Christiana eDimitropoulou
Qing eLu
Stephen M Black
Shruti eSharma
author_sort Saurabh eAggarwal
collection DOAJ
description Acute lung injury (ALI) is a life threatening condition associated with hypoxemia, diffuse alveolar damage, inflammation, and loss of lung function. Lipopolysaccharide (LPS; endotoxin) from the outer membrane of gram-negative bacteria is a major virulence factor involved in the development of ALI. The depletion of glutathione (GSH), an essential intra- and extra- cellular protective antioxidant, by LPS is an important event that contributes to the elevation in reactive oxygen species. Whether restoring GSH homeostasis can effectively ameliorate mitochondrial dysfunction and cellular apoptosis in ALI is unknown and therefore, was the focus of this study. In peripheral lung tissue of LPS-treated mice, hydrogen peroxide, peroxynitrite, and protein nitration levels were all significantly increased. Pre-treatment with GSH ethyl ester (GSH-EE) prevented this increase in oxidative stress. LPS also increased the lactate/pyruvate ratio, attenuated SOD2 protein levels, and decreased ATP levels in the mouse lung indicative of mitochondrial dysfunction. Again GSH-EE treatment preserved mitochondrial function. Finally, our studies showed that LPS induced an increase in the mitochondrial translocation of Bax, caspase-3 activation, and nuclear DNA fragmentation and these parameters were all prevented with GSH-EE. Thus, this study suggests that GSH-EE supplementation may reduce the mitochondrial dysfunction associated with ALI.
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spelling doaj.art-7ba227110ad842aaab74955a5d19aa0f2022-12-22T01:06:15ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2012-05-01310.3389/fphys.2012.0016123040Glutathione Supplementation Attenuates Lipopolysaccharide-induced Mitochondrial Dysfunction and Apoptosis in a Mouse Model of Acute Lung InjurySaurabh eAggarwal0Christiana eDimitropoulou1Qing eLu2Stephen M Black3Shruti eSharma4Georgia Health Sciences UniversityGeorgia Health Sciences UniversityGeorgia Health Sciences UniversityGeorgia Health Sciences UniversityGeorgia Health Sciences UniversityAcute lung injury (ALI) is a life threatening condition associated with hypoxemia, diffuse alveolar damage, inflammation, and loss of lung function. Lipopolysaccharide (LPS; endotoxin) from the outer membrane of gram-negative bacteria is a major virulence factor involved in the development of ALI. The depletion of glutathione (GSH), an essential intra- and extra- cellular protective antioxidant, by LPS is an important event that contributes to the elevation in reactive oxygen species. Whether restoring GSH homeostasis can effectively ameliorate mitochondrial dysfunction and cellular apoptosis in ALI is unknown and therefore, was the focus of this study. In peripheral lung tissue of LPS-treated mice, hydrogen peroxide, peroxynitrite, and protein nitration levels were all significantly increased. Pre-treatment with GSH ethyl ester (GSH-EE) prevented this increase in oxidative stress. LPS also increased the lactate/pyruvate ratio, attenuated SOD2 protein levels, and decreased ATP levels in the mouse lung indicative of mitochondrial dysfunction. Again GSH-EE treatment preserved mitochondrial function. Finally, our studies showed that LPS induced an increase in the mitochondrial translocation of Bax, caspase-3 activation, and nuclear DNA fragmentation and these parameters were all prevented with GSH-EE. Thus, this study suggests that GSH-EE supplementation may reduce the mitochondrial dysfunction associated with ALI.http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00161/fullAcute Lung InjuryApoptosislipopolysaccharideMitochondrial dysfunctionGlutathione ethyl ester
spellingShingle Saurabh eAggarwal
Christiana eDimitropoulou
Qing eLu
Stephen M Black
Shruti eSharma
Glutathione Supplementation Attenuates Lipopolysaccharide-induced Mitochondrial Dysfunction and Apoptosis in a Mouse Model of Acute Lung Injury
Frontiers in Physiology
Acute Lung Injury
Apoptosis
lipopolysaccharide
Mitochondrial dysfunction
Glutathione ethyl ester
title Glutathione Supplementation Attenuates Lipopolysaccharide-induced Mitochondrial Dysfunction and Apoptosis in a Mouse Model of Acute Lung Injury
title_full Glutathione Supplementation Attenuates Lipopolysaccharide-induced Mitochondrial Dysfunction and Apoptosis in a Mouse Model of Acute Lung Injury
title_fullStr Glutathione Supplementation Attenuates Lipopolysaccharide-induced Mitochondrial Dysfunction and Apoptosis in a Mouse Model of Acute Lung Injury
title_full_unstemmed Glutathione Supplementation Attenuates Lipopolysaccharide-induced Mitochondrial Dysfunction and Apoptosis in a Mouse Model of Acute Lung Injury
title_short Glutathione Supplementation Attenuates Lipopolysaccharide-induced Mitochondrial Dysfunction and Apoptosis in a Mouse Model of Acute Lung Injury
title_sort glutathione supplementation attenuates lipopolysaccharide induced mitochondrial dysfunction and apoptosis in a mouse model of acute lung injury
topic Acute Lung Injury
Apoptosis
lipopolysaccharide
Mitochondrial dysfunction
Glutathione ethyl ester
url http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00161/full
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