Mansour H, Brun-Pascaud M, Marquetty C, Gougerot-Pocidalo M A, Hakim J, Pocidalo J J
INSERM U.13, Hôpital Claude Bernard, Paris, France.
Am Rev Respir Dis. 1988 Mar;137(3):688-94. doi: 10.1164/ajrccm/137.3.688.
Rats were pretreated with various inducers of cytochrome P-450 before being exposed to pure normobaric oxygen (O2) in order to determine whether the inducers interfere with toxicity. The pulmonary and liver inducers beta-naphthoflavone (beta NF) and 3-methylcholanthrene (3MC) increased the survival rate and decreased the amount of pleural and lung fluid accumulation in adult rats exposed to oxygen. Phenobarbital (PB), which is essentially active in the hepatic microsomal cytochrome P-450, was less effective in counteracting oxygen toxicity. After 7 days of exposure to oxygen, none of the untreated rats survived, whereas 40, 73, and 90% survival was observed in rats treated with PB, 3MC, and beta NF, respectively. After 60 h of O2 exposure, significantly less pleural and lung fluid accumulation was observed in beta NF- and 3MC-treated rats than in untreated or PB-treated rats (p less than 0.001). Both beta NF and 3MC prevented the increase of lung peroxidation (assessed by measuring of malondialdehyde) and that of hydrogen peroxide production by lung microsomes induced by O2 exposure. These protective effects are associated with a large increase in the components of the pulmonary cytochrome P-450 system and its peroxidase activity and with an increased response to hyperoxia by lung antioxidant enzyme activities. In contrast, in control rats, the activities of the antioxidant enzymes were not increased, and both the quantity and the peroxidase activity of cytochrome P-450 were significantly decreased by O2 exposure. We conclude that in the rat, pretreatment by inducers of pulmonary cytochrome P-450 results in marked protection against O2 toxicity and an increase of antioxidant enzyme response to hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
在将大鼠暴露于纯常压氧（O₂）之前，先用各种细胞色素P - 450诱导剂对其进行预处理，以确定这些诱导剂是否会干扰毒性。肺部和肝脏诱导剂β - 萘黄酮（βNF）和3 - 甲基胆蒽（3MC）提高了成年大鼠暴露于氧气时的存活率，并减少了胸腔和肺内液体的积聚量。主要在肝微粒体细胞色素P - 450中起作用的苯巴比妥（PB）在对抗氧毒性方面效果较差。暴露于氧气7天后，未处理的大鼠无一存活，而用PB、3MC和βNF处理的大鼠存活率分别为40%、73%和90%。暴露于O₂ 60小时后，与未处理或PB处理的大鼠相比，βNF和3MC处理的大鼠胸腔和肺内液体积聚明显减少（p < 0.001）。βNF和3MC均能阻止肺过氧化的增加（通过测量丙二醛评估）以及由O₂暴露诱导的肺微粒体过氧化氢生成的增加。这些保护作用与肺细胞色素P - 450系统成分及其过氧化物酶活性的大幅增加以及肺抗氧化酶活性对高氧反应的增强有关。相比之下，在对照大鼠中，抗氧化酶的活性没有增加，细胞色素P - 450的量和过氧化物酶活性均因O₂暴露而显著降低。我们得出结论，在大鼠中，用肺细胞色素P - 450诱导剂进行预处理可显著保护其免受O₂毒性，并增加抗氧化酶对高氧的反应。（摘要截短至250字）
