The effects of
cytochrome P-450 inducers on O2 toxicity were studied in mice. We first examined three
cytochrome P-450 inducers, which differ by their specific tissue affinity:
phenobarbital sodium (PB), essentially active in the liver, and
3-methylcholanthrene (3-MC) and
beta-naphthoflavone (BNF), which are also active in the lung. Both BNF and 3-MC increased the survival rate and significantly decreased
pulmonary edema (pulmonary water and wet-to-dry weight ratio) in C57BL/6J mice exposed to
hyperoxia (O2 greater than or equal to 95%), whereas PB had no protective effect. In the second part of this study, we compared the action of BNF in two strains of mice. In one (C57BL/6J),
cytochrome P-450 can be induced by
aromatic hydrocarbons, whereas in the other (DBA/2J)
cytochrome P-450 is not inducible by these compounds. Protection against O2 toxicity was assessed in terms of lethality and
pulmonary edema and of lung lipid peroxidation (assessed by measuring
malondialdehyde). BNF only protected against O2 toxicity in the inducible strain. This protective effect of BNF on O2 toxicity in C57BL/6J mice was associated mainly with a large increase in the components of the
cytochrome P-450 system (
cytochrome P-450 and
cytochrome b5) in the lung. The activity of pulmonary
superoxide dismutase was also slightly increased, but the enhancement was not statistically significant. In contrast, in DBA/2J mice neither the components of the
cytochrome P-450 system nor the activity of
superoxide dismutase showed any increase.(ABSTRACT TRUNCATED AT 250 WORDS)