Concentration of 3-methylindole (3MI) and distribution of radioactivity from 14C-3MI in goat tissues associated with acute pulmonary edema.
3-Methylindole (3MI) can cause acute pulmonary edema in goats. Because of known lipophilic properties and direct effects on biological membranes, the concentration of 3MI and distribution of radioactivity from 14C-3MI in tissues was investigated during development of 3MI-induced APE. Goats were given a 2 hr jugular infusion of 3MI containing 14C-3MI using propylene glycol as the vehicle. Groups of 3 goats were killed at 0, 5, 2 and 4 hr and 2 goats were killed at 8 and 24 hr. Plasma, lung, liver, kidney and other selected tissues were collected. 3MI was rapidly cleared from blood plasma and tissues after infusion, and 81% of the radioactivity was excreted in the urine by 24 hr. Maximum concentrations of unmetabolized 3MI in the tissues ranged from 2.6 to 15 micrograms 3MI/g, including 7.5 micrograms 3MI/g in the lung. The ratios of equivalent radioactivity to unmetabolized eMI indicated rapid metabolism and the presence of metabolites in all tissues studied. The lung contained the highest proportion of metabolites with ratios of radioactivity to unmetabolized 3MI of about 50, 10, 250, 150 and 80 at 0.5, 2, 4, 8 and 24 hr. The data demonstrate that 3MI does not selectively concentrate in the lung and that the concentrations are lower than those usually associated with direct membrane damage. They also indicate that 3MI is rapidly metabolized and that metabolites are present in tissues, especially the lung. These results suggest that direct effects of 3MI on biological membranes are not primarily responsible for lung injury in goats.
D000818:Animals; D006041:Goats; D007211:Indoles / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism*; D012862:Skatole / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D007211:Indoles; D012862:Skatole