Pharmacokinetics in hepatic transport of amaranth in rats intoxicated with carbon tetrachloride and .ALPHA.-naphthylisothiocyanate.

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The hepatic transport of amaranth (AM) was investigated in normal rats and rats with hepatic intoxication induced by subcutaneous or oral administration of carbon tetrachloride (CCl4s. c. or CCl4p. o.) or by oral administration of α-naphthylisothiocyanate (ANIT). The kinetics of the disappearance of AM from plasma as well as the kinetics of its appearance in the bile were studied in rats under pentobarbital anesthesia and the binding activities of plasma and hepatic cytoplasmic proteins to AM were also investigated. A retarded plasma disappearance of AM was observed in CCl4-or ANIT-intoxicated rats and biliary excretion of AM was decreased in CCl4-intoxicated rats. Bile flow and biliary excretion of AM were not observed in ANIT-intoxicated rats. The total amount of AM bound to the plasma protein was decreased in ANIT-intoxicated rats, but was not affected in CCl4-intoxicated groups. The pharmacokinetic parameters were calculated with a three-compartment model, and a decrease in k12 (transfer rate constant from plasma to liver) and k23 (transfer rate constant from liver to bile) were observed in CCl4p. o.-intoxicated rats. In CCl4s. c.-intoxicated rats, only k12 was decreased. In ANIT-intoxicated rats, significant decreases in k12 and increases in k24 (rate constant of metabolism) were observed. AM was bound preferentially to X-and Y-fraction rather than to Z-fraction in cytoplasmic proteins. Although the protein concentration in the 110000g supernatant and in the Y-fraction was decreased in CCl4p. o.-intoxicated rats, the total protein content of whole liver was not affected. It was considered that changes in the hepatic plasma flow may be a main cause of the retarded disappearance of AM from plasma in the intoxicated rats.

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