Toxicity of 3-Methyleneoxindole, a Proposed Reactive Intermediate in the Metabolism of 3-Methylindole
3-Methylindole (3MI) is constitutively produced by anaerobic bacterial fermentation of tryptophan in mammalian intestines. In the case of ruminants excessive 3MI production causes selective pulmonary toxicity which can be fatal (Carlson and Yost, 1989; Yost, 1989). Previous work with ruminants has demonstrated that type I alveolar epithelial and nonciliated bronchiolar epithelial (Clara) cells are the most susceptible pulmonary cells. It has been suggested (Yost, 1989) that this pneumotoxicity results from cytochrome P-450 activation of 3MI to reactive intermediates (Figure 1) which react with macromolecules to produce the toxicity. One of the proposed intermediates is 3-methyleneoxindole (MEOI) which is known to react covalently with sulfhydryl groups (Still et al., 1965). This paper presents in vivo and in vitro findings about the toxicity of MEOI.
KeywordsReactive Intermediate Indole Derivative Rabbit Lung Electron Impact Mass Spectrometry Pulmonary Cell
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