Foth H
Department of Pharmacology and Toxicology, University of Göttingen, Germany.
Crit Rev Toxicol. 1995;25(2):165-205. doi: 10.3109/10408449509021612.
The mammalian lung is exposed to and affected by many airborne and bloodborne foreign compounds. This review summarizes the role of lung in accumulation and metabolism of xenobiotics, some of which are spontaneously reactive or are metabolically activated to toxic intermediates. The specific architectural arrangement of mammalian lung favors that so-called pneumophilic drugs are filtered out of the blood and are retained within the tissue as shown in particular for amphetamine, chlorphentermine, amiodarone, imipramine, chlorpromazine, propranolol, local anaesthetics, and some miscellaneous therapeutics. There is strong evidence that intrapulmonary distribution activity and regulation of drug-metabolizing enzymes in lung is distinct from liver. This review focuses on the metabolic rate of selected compounds in lung such as 5-fluoro-2'-deoxyuridine, local anesthetics, nicotine, benzo(alpha)pyrene, ipomeanol, 4-methylnitrosamino-1-(3-pyridyl)-1-butanone. It is widely accepted that the formation of radical species is a key event in the pneumotoxic mechanisms induced by bleomycin, paraquat, 3-methylindole, butylhydroxytoluene, or nitrofurantoin. Finally, methodological approaches to assess the capacity of lung to eliminate foreign compounds as well as biochemical features of the pulmonary tissue are evaluated briefly.
哺乳动物的肺会接触到多种空气传播和血源性病原体，并受其影响。本综述总结了肺在异生物素蓄积和代谢中的作用，其中一些异生物素具有自发反应性或经代谢活化形成有毒中间体。哺乳动物肺的特定结构布局有利于将所谓的亲肺性药物从血液中滤出并保留在组织内，如苯丙胺、氯苯丁胺、胺碘酮、丙咪嗪、氯丙嗪、普萘洛尔、局部麻醉药及其他一些治疗药物的情况所示。有充分证据表明，肺内药物分布活性及肺内药物代谢酶的调节与肝脏不同。本综述重点关注肺中选定化合物的代谢率，如5-氟-2'-脱氧尿苷、局部麻醉药、尼古丁、苯并(α)芘、异戊二烯醇、4-甲基亚硝胺-1-(3-吡啶基)-1-丁酮。人们普遍认为，自由基的形成是博来霉素、百草枯、3-甲基吲哚、丁基羟基甲苯或呋喃妥因诱导的肺毒性机制中的关键事件。最后，简要评估了评估肺清除外来化合物能力的方法以及肺组织的生化特征。
