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| Abstract |
While it has been reported that the blood level of dioxins and polychlorinated biphenyls in humans may be decreased by treatment with colestimide, the effects of the agent are still obscure. To addres...s this issue, we examined the effect of Cholebine, a cholesterol lowering agent containing colestimide as an active ingredient, on the excretion of 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) in rats. In a short term study, male Wistar rats (5 weeks-old) were given chows including 3% Cholebine (PenCDF/Chol group) or control chows (PenCDF group) for 7 days after administration of 14C-labeled PenCDF (0.5 mg/kg body weight, p.o.). On day 1, the fecal excretion of PenCDF in the PenCDF/Chol group was greater by 15% compared to that of the PenCDF group. Although some increases were also observed during day 2 and day 7, Cholebine did not exhibit any marked effect on the fecal excretion of PenCDF. The tissue concentrations of PenCDF at day 7 in the PenCDF/Chol group showed a 20%.30% decrease compared with those of the PenCDF group, except that the level in the brain was comparable between the two groups. The fecal excretion of PenCDF in a long term study (Cholebine treatment for 28 days) demonstrated the same tendency as that of short term study. However, in long term study, the Cholebine had no effect on the tissue concentration of PenCDF except for brain. An increase in PenCDF excretion by Cholebine seems to be due to the binding of Cholebine to bile acids as lipid carriers. This is because no binding of Cholebine to 14C-PenCDF was detected. These results suggest that Cholebine has little effect on the reabsorption of dioxin, whereas it reduces substantially the first absorption of dioxin.show more
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