Role of the lung in accumulation and metabolism of xenobiotic compounds--implications for chemically induced toxicity

Abstract

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.