Position of Perilla Ketone Metabolism by Lung Cytochromes P450: Evidence for the Mechanism of Bioactivation Through Design of an In Vivo Inhibitor of Toxicity

Serious pulmonary damage can arise in many animal species from a variety of naturally occurring five-membered heterocycles. But the greatest acute risk seems associated with those bearing 3-substituents (Garst and Wilson, 1981; Garst et al., 1985; Kerr and Linnabary, 1989; Wilson et al., 1990). For example, in susceptible species, acute and often lethal pulmonary edema quickly arises from ingestion of foodstuffs containing the furans 4-ipomeanol [1-(3-furyl)-4-hydroxypentan-l-one] and perilla ketone ([1]) [1-(3-furyl)-4-methyl-pentan-1-one]. 4-Ipomeanol is one of several constituents in moldy sweet potatoes (Wilson et al., 1978). Perilla ketone ([1]) and related unsaturated derivatives are constituents of the mint plant Perilla frutescens (Garst and Wilson, 1984). Similar toxicity results when animals consume large quantities of the 3-substituted indole, tryptophan, although this amino acid must first be transformed to 3-methylindole (3MI) (Nocerini et al., 1984, 1985a,b).