Frank L
Fed Proc. 1985 Apr;44(7):2328-34.
The free radical theory of O2 toxicity provides a testable explanation of the mechanism of O2's toxic effects on a biochemical and cellular level. In addition, it provides for an understanding of the array of normal antioxidant defenses of the cell and an insight to rational approaches to pharmacologic prophylaxis against clinical O2 toxicity. Neonatal animals of many species are much more resistant to the lethal effects of exposure to high concentrations of O2 than are the adult animals of the species; this increased tolerance is associated with the newborn lungs' ability to increase its normal complement of protective antioxidant enzymes during O2 exposure. Premature infants who require vigorous hyperoxic respiratory support early in life frequently develop acute and chronic lung changes compatible with pulmonary O2 toxicity, so-called bronchopulmonary dysplasia. The lung of the prematurely born may be quite ill-adapted for protecting itself against hyperoxic exposure owing to immaturity of its antioxidant defensive systems. Clinical pharmacologic stratagems designed to augment the intracellular antioxidant defensive capacity of the lung may become available in the near future, which would provide some means to prevent or ameliorate the serious lung damage associated with the clinical use of life-giving O2.
氧中毒的自由基理论为氧在生化和细胞水平上产生毒性作用的机制提供了一个可检验的解释。此外,它有助于理解细胞正常的抗氧化防御机制,并为预防临床氧中毒的合理药理学方法提供思路。许多物种的新生动物比该物种的成年动物对高浓度氧暴露的致死作用具有更强的抵抗力;这种耐受性的增加与新生肺在氧暴露期间增加其正常的保护性抗氧化酶补充的能力有关。生命早期需要积极高氧呼吸支持的早产儿经常出现与肺氧中毒相符的急性和慢性肺部变化,即所谓的支气管肺发育不良。由于其抗氧化防御系统不成熟,早产儿的肺可能极不适应保护自身免受高氧暴露。旨在增强肺细胞内抗氧化防御能力的临床药理学策略可能在不久的将来出现,这将提供一些手段来预防或改善与使用维持生命的氧相关的严重肺损伤。