Electrophilic metabolites of 3-methylindole as toxic intermediates in pulmonary oedema

Abstract

1. [methyl-¹⁴C]-3-Methylindole (3MI) was incubated with goat-lung microsomes, an NADPH-generating system and glutathione.

2. An adduct between an oxidative metabolite of 3MI and glutathione was formed only when the complete system was employed.

3. The adduct, which was detected by u.v. absorbance and scintillation counting of h.p.l.c. fractions, was purified to homogeneity by reverse-phase h.p.l.c.

4. The ability of 3MI to bind to microsomal protein was reduced to 52% and 46% of controls when 2mM and 4mM glutathione, respectively, were included in the incubations.

5. These results suggest the involvement of an electrophilic metabolite as the toxic intermediate in 3MI-mediated pulmonary oedema.