Mice Deficient in the Gene for Cytochrome P450 (CYP)1A1 are More Susceptible than Wild-Type to Hyperoxic Lung Injury: Evidence for Protective Role of CYP1A1 Against Oxidative Stress

Abstract

Hyperoxia contributes to acute lung injury in diseases such as acute respiratory distress syndrome in adults and bron-chopulmonary dysplasia in premature infants. Cytochrome P450 (CYP)1A1 has been shown to modulate hyperoxic lung injury. The mechanistic role(s) of CYP1A1 in hyperoxic lung injury in vivo is not known. In this investigation, we hypothesized that Cyp1a1(–/–) mice would be more susceptible to hyperoxic lung injury than wild-type (WT) mice, and that the protective role of CYP1A1 is in part due to CYP1A1-mediated decrease in the levels of reactive oxygen species-mediated lipid hydroperoxides, e.g., F2-isoprostanes/isofurans, leading to attenuation of oxidative dam-age. Eight- to ten-week-old male WT (C57BL/6J) or Cyp1a1(–/–) mice were exposed to hyperoxia (>95 % O2) or room air for 24– 72 h. The Cyp1a1(–/–) mice were more susceptible to oxygen-mediated lung damage and inflammation than WT mice, as evi