Overexpression of manganese superoxide dismutase by N-acetylcysteine in hyperoxic lung injury.
BACKGROUND
Exposure of animals to hyperoxia causes lung injury, characterized by diffuse alveolar damage and exudation of plasma into the alveolar space. Reactive oxygen species (ROS) play an important role in the development of hyperoxic lung injury. Mitochondrial oxidative phosphorylation is one of the major sources of ROS. N-acetylcysteine (NAC) is a precursor of glutathione (GSH), which functions as an antioxidant by reducing hydrogen peroxide to water and alcohols. NAC has been shown to diminish lung injury in a large variety of animal models.


OBJECTIVE
We elucidated the mechanism underlying the protective effects of NAC in hyperoxia-induced lung injury.


METHODS
Male BALB/c mice were exposed to 98% oxygen for 72 h. The mice inhaled NAC or saline twice a day from 72 h before oxygen exposure to the end of experiment.


RESULTS
Inhaled NAC increased the GSH level in lung homogenate. NAC also attenuated cellular infiltrations in both bronchoalveolar lavage fluid (BALF) and lung tissue. The total protein level in BALF and the level of 8-isoprostane, a marker of lipid peroxidation, in lung homogenate were decreased by inhalation of NAC. Inhaled NAC induced the overexpression of Mn superoxide dismutase (MnSOD) mRNA and protein, but did not alter the expressions of other antioxidant enzymes, including CuZnSOD, extracellular SOD, and glutathione peroxydase 1.


CONCLUSIONS
These findings suggest that the antioxidant properties of NAC in hyperoxic lung injury involve a decrease in mitochondrial ROS in association with the induction of MnSOD, in addition to its role as a precursor of GSH.
Nagata
Kazuhiro
K
Department of Respiratory Medicine, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. nagata@koto.kpu-m.ac.jp
Iwasaki
Yoshinobu
Y
Yamada
Tadaaki
T
Yuba
Tatsuya
T
Kono
Kenji
K
Hosogi
Shigekuni
S
Ohsugi
Shuji
S
Kuwahara
Hiroomi
H
Marunaka
Yoshinori
Y
D000111:Acetylcysteine / Q000008:administration & dosage*; D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002452:Cell Count; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D005978:Glutathione / Q000032:analysis; D018496:Hyperoxia / Q000201:enzymology*; D015227:Lipid Peroxidation / Q000502:physiology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013482:Superoxide Dismutase / Q000032:analysis*
D000336:Aerosols; D016166:Free Radical Scavengers; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine