Time course of inflammation, oxidative stress and tissue damage induced by hyperoxia in mouse lungs.
In this study our aim was to investigate the time courses of inflammation, oxidative stress and tissue damage after hyperoxia in the mouse lung. Groups of BALB/c mice were exposed to 100% oxygen in a chamber for 12, 24 or 48 h. The controls were subjected to normoxia. The results showed that IL-6 increased progressively after 12 (P < 0.001) and 24 h (P < 0.001) of hyperoxia with a reduction at 48 h (P < 0.01), whereas TNF-α increased after 24 (P < 0.001) and 48 h (P < 0.001). The number of macrophages increased after 24 h (P < 0.001), whereas the number of neutrophils increased after 24 h (P < 0.01) and 48 h (P < 0.001). Superoxide dismutase activity decreased in all groups exposed to hyperoxia (P < 0.01). Catalase activity increased only at 48 h (P < 0.001). The reduced glutathione/oxidized glutathione ratio decreased after 12 h (P < 0.01) and 24 h (P < 0.05). Histological evidence of lung injury was observed at 24 and 48 h. This study shows that hyperoxia initially causes an inflammatory response at 12 h, resulting in inflammation associated with the oxidative response at 24 h and culminating in histological damage at 48 h. Knowledge of the time course of inflammation and oxidative stress prior to histological evidence of acute lung injury can improve the safety of oxygen therapy in patients.
Laboratório de Reparo Tecidual, Departamento de Histologia e Embriologia, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Akinori C
AC
Nagato
Frank S
FS
Bezerra
Manuella
M
Lanzetti
Alan A
AA
Lopes
Marco Aurélio S
MA
Silva
Luís Cristóvão
LC
Porto
Samuel S
SS
Valença
D000818:Animals; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D018496:Hyperoxia / Q000150:complications*; D007249:Inflammation / Q000209:etiology* / Q000503:physiopathology*; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002374:Catalase; D013482:Superoxide Dismutase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D005978:Glutathione; D010100:Oxygen; D019803:Glutathione Disulfide