Age difference in the metabolism of p-bromophenylacetylurea in the rat: Animplication for age-related susceptibility to its neurotoxicity

p-Bromophenylacetylurea (BPAU)-induced delayed neuropathy showed an age-dep endent susceptibility in rats. This study investigated the difference in BP AU metabolism in rats of two different ages to explore the metabolic aspect in age-dependent susceptibility to BPAU-induced neurotoxicity. Either 6-we ek or 1-year old F344 male rats (n = 4) were given a single oral dose of 15 0 mg/kg BPAU. BPAU and its metabolites, N'- hydroxy-p-bromophenylacetylurea (HBPAU) and 4-(4-bromophenyl)-3-oxapyrrolidine-2,5 dione (BPOPD), in serum , liver, brain and spinal cord were determined by HPLC 18 hr after dosing. The results showed that the levels of BPAU and HBPAU in the tissues of 1-ye ar old rats were generally higher than those in the corresponding tissues o f 6-week old rats. The levels of both BPAU and HBPAU in the spinal cord of the 1-year old rats were higher than those of the 6-week old rats (p < 0.05 ). In the serum, the concentration of BPOPD in the 6-week old rats was high er than that in the 1-year old rats (p < 0.01) whereas the HBPAU levels in the serum of 6-week old rats was significantly lower than that in the 1-yea r old rats (p < 0.05). Thus the 6-week old rats metabolized BPAU more effic iently by producing more BPOPD, a detoxified metabolite, and less HBPAU, a suspected toxic metabolite, than the 1-year old rats. This suggests that th e same dosage of BPAU may produce less severe initial lesions in young anim als than in adults, and hence young animals exhibit more resistance to BPAU -induced neurotoxicity than adult rats. Therefore, metabolic differences be tween young and adult rats may be responsible for their age-related suscept ibility to BPAU-induced neurotoxicity. (C) 2000 Intox Press, Inc.