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 address 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.