Disruption of the Ah receptor gene alters the susceptibility of mice to oxygen-mediated regulation of pulmonary and hepatic cytochromes P4501A expression and exacerbates hyperoxic lung injury

摘要: Administration of supplemental oxygen is frequently encountered in infants suffering from pulmonary insufficiency and adults with acute respiratory distress syndrome. However, hyperoxia causes lung damage experimental animals. In the present study, we investigated roles Ah receptor (AHR) modulation cytochrome P4501A (CYP1A) enzymes development injury by hyperoxia. Adult male wild-type [AHR (+/+)] mice AHR-deficient animals (-/-)] were maintained room air or exposed to (>95% oxygen) for 24 72 h, hepatic expression CYP1A studied. Hyperoxia caused significant increases CYP1A1 activities (ethoxyresorufin O-deethylase) mRNA levels (C57BL/6J) AHR (+/+), but not (-/-) mice, suggesting that AHR-dependent mechanisms contributed induction. On other hand, augmented CYP1A2 both animals, AHR-independent regulation more susceptible than inflammation, as indicated significantly higher weight/body weight ratios, increased edema, enhanced neutrophil recruitment into lungs. conclusion, our results support hypothesis induces CYP1A1, CYP1A2, vivo mechanisms, a phenomenon may mechanistically contribute beneficial effects hyperoxic injury.