Age-related sensitivity to lung oxidative stress during ozone exposure.
As immature and aged rats could be more sensitive to ozone (O(3))-linked lung oxidative stress we have attempted to shed more light on age-related susceptibility to O(3) with focusing our interest on lung mitochondrial respiration, reactive oxygen species (ROS) production and lung pro/antioxidant status. For this purpose, we exposed to fresh air or O(3) (500 ppb 12 h per day, for 7 days) 3 week- (immature), 6 month- (adult) and 20 month-old rats (aged). We determined, in lung, H(2)O(2) release by mitochondria, activities of major antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT)], heat shock protein (HSP(72)) content and 8-oxodG and dG-HNE nDNA contents, as DNA oxidative damage markers. In adult rats we did not observe alteration of pro/antioxidant status. In contrast to adults, immature rats exposed to O(3) higher nDNA 8-oxodG content and HSP(72) and without antioxidant enzymes modification. Aged rats displayed mild uncoupled lung mitochondria, increased SOD and GPx activities, and higher 8-oxodG content after O(3) exposure. Thus, in contrast to adults, immature and aged rats displayed lung oxidative stress after O(3) exposure. Higher sensitivity of immature to O(3) was partly related to ventilatory parameters and to the absence of antioxidant enzyme response. In aged rats, the increase in cytosolic SOD and GPx activities during O(3) exposure was not sufficient to prevent the impairment in mitochondrial function and accumulation in lung 8- oxodG. Finally, we showed that mitochondria seem not to be a major source of ROS under O(3) exposure.
Servais
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S
Unité Mixte de Recherche 5123 CNRS, Laboratoire de Physiologie Intégative Cellulaire et Moléclaire, Université Claude Bernard, Lyon, France. stephane.servais@univ-lyon1.fr
Boussouar
A
A
Molnar
A
A
Douki
T
T
Pequignot
J M
JM
Favier
R
R
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010126:Ozone / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012119:Respiration; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D010083:Oxidants, Photochemical; D017382:Reactive Oxygen Species; D010126:Ozone; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine