The metabolic basis of 3-methylindole-induced pneumotoxicity.
3-Methylindole (3MI), an abnormal metabolite of tryptophan, causes acute pulmonary edema and emphysema. 3MI toxicity is species-, tissue- and cell-specific and is an excellent model for understanding the processes of chemically-induced lung injury. Experimental evidence showed that 3MI is metabolically activated by both microsomal cytochrome P-450-dependent mixed function oxidase (MFO) and prostaglandin H synthase (PHS) systems in the lung. Formation of a free radical intermediate during 3MI metabolism is the initial chemical event which is responsible for the pneumotoxicity. 3MI free radicals bind covalently to microsomal protein and induce lipid peroxidation. Microsomal enzymes which regulate the glycogen and phospholipid biosynthesis in the lung are altered during the cellular repair processes after 3MI-induced lung injury. Inhibition of cellular differentiation from Type II to Type I cells and impaired surfactant function may be crucial to the disease process.
Bray
T M
TM
Department of Nutritional Sciences, University of Guelph, Ontario, Canada.
Kirkland
J B
JB
D000818:Animals; D001711:Biotransformation; D006801:Humans; D007211:Indoles / Q000633:toxicity*; D008171:Lung Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D012862:Skatole / Q000633:toxicity*
D007211:Indoles; D012862:Skatole; D006899:Mixed Function Oxygenases