Metabolism of trans-stilbene in rabbits and rats.

The biotransformation of intramuscularly administered 14C-labeled trans-stilbene was investigated in both rabbits and rats. In rabbits radioactivity was excreted (78.8% in 17 days) almost exclusively in the urine. In rats, feces accounted for more than half of the total excretion (80.3% in 19 days). Hydroxylated metabolites in urine and feces were identified by thin-layer chromatography and quantitated by liquid scintillation counting. They were 4-hydroxy and 4,4'-dihydroxystilbene, and the two monomethyl ethers of 3,4-dihydroxystilbene and 4,4'-dihydroxybibenzyl. In addition, four polyhydroxylated metabolites of stilbene and bibenzyl were identified in rat urine by comparison of gas-liquid chromatography retention times of their silyl derivatives with synthetic reference compounds. They were 3,4,4'-trihydroxystilbene, and 3,4-dihydroxy-, 3,4,4'=trihydroxy-, and 3,4,3',4'-tetrahydroxybibenzyl. Oxidative cleavage of trans-stilbene to benzoic acid and 4-hydroxy- and 3,4-dihydroxybenzoic acid was established by the presence of both the free acids and conjugates of these compounds in both rabbit and rat urine. Their glycine conjugates were identified by thin-layer chromatography and quantitated by reverse isotope dilution procedures from unhydrolyzed rabbit and rat urine. Percentages obtained indicate that cleavage of trans-stilbene is more extensive in rabbits (9.5%) than in rats (2.7%).