Age difference in the metabolism of p-bromophenylacetylurea in the rat: an implication for age-related susceptibility to its neurotoxicity.
p-Bromophenylacetylurea (BPAU)-induced delayed neuropathy showed an age-dependent susceptibility in rats. This study investigated the difference in BPAU metabolism in rats of two different ages to explore the metabolic aspect in age-dependent susceptibility to BPAU-induced neurotoxicity. Either 6-week or 1-year old F344 male rats (n = 4) were given a single oral dose of 150 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-year old rats were generally higher than those in the corresponding tissues of 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 higher 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-year old rats (p < 0.05). Thus the 6-week old rats metabolized BPAU more efficiently by producing more BPOPD, a detoxified metabolite, and less HBPAU, a suspected toxic metabolite, than the 1-year old rats. This suggests that the same dosage of BPAU may produce less severe initial lesions in young animals than in adults, and hence young animals exhibit more resistance to BPAU-induced neurotoxicity than adult rats. Therefore, metabolic differences between young and adult rats may be responsible for their age-related susceptibility to BPAU-induced neurotoxicity.
Xu
J
J
Department of Biological and Biomedical Sciences, Faculty of Applied Sciences, University of the West of England, Bristol, United Kingdom. jinsheng.xu@uwe.ac.uk
Purcell
W M
WM
Ray
D E
DE
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000378:metabolism*; D008297:Male; D009498:Neurotoxins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000378:metabolism*; D014508:Urea / Q000031:analogs & derivatives* / Q000378:metabolism
D009498:Neurotoxins; C004506:4-bromophenylacetylurea; D014508:Urea