Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intestinal absorption of mizoribine, an imidazole nucleoside, is mediated by concentrative nucleoside transporter (CNT)1 and CNT2 in rat. Previously, bile and bile salts such as sodium glycocholate were found to suppress the intestinal absorption of mizoribine. In the present study, the contribution of bile on the intestinal absorption of mizoribine was further evaluated in rats. Cholestatic states were induced by an intraperitoneal injection (2 ml/kg) of 50% carbon tetrachloride (CCl4) dissolved in olive oil, or oral administration (100 mg/2 ml/kg) of alpha-naphthylisothiocyanate (ANIT) dissolved in olive oil. The animals were subjected to absorption studies 24 h after treatment. Cholestatic states were confirmed by measuring plasma concentrations of bile acids and bile flow rates. When oral bioavailability of mizoribine was estimated by the recovery amount in the urine, rats under cholestatic states exhibited significantly higher oral bioavailabilities than untreated control rats. In contrast, the intestinal absorption percentages of mizoribine from in-situ lavaged intestinal loops were the same magnitudes among untreated control, CCl4- and ANIT-treated rats. These results indicated that the increased oral bioavailability of mizoribine in cholestatic rats was not ascribed to the modulation of nucleoside transporter's expression. In conclusion, various diseased states accompanied with cholestasis may increase the oral bioavailability of mizoribine, possibly due to its less amounts of bile in the intestinal lumen.
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PMID:Increased intestinal absorption of mizoribine, an immunosuppressive agent, in cholestatic rats. 2066 10

The characteristics of intestinal absorption of mizoribine and cephalexin, that are mediated by concentrative nucleoside transporters (CNTs) and PEPT1, respectively, was examined in lipopolysaccharide (LPS)-treated rats. LPS treatment is known to modify the expression of some transporters and induce cholestasis. At 24 h after the LPS treatment, averaged concentrations of IL-6 and total bile acids in plasma were 15-fold and 2-fold that in untreated control rats, respectively, and bile flow rate decreased by 40% of control, indicating the induction of inflammatory and cholestatic states. The oral bioavailability, estimated by urinary excretion percentage of unchanged form, of mizoribine in LPS-treated rats was 1.5-fold higher than that in control rats, whereas the bioavailability of cephalexin remained unchanged. When mizoribine and cephalexin were administered into in-situ jejunum loops, there were no differences in the absorption rates between control and LPS-treated rats. These results indicated that the functional expression of CNT1, CNT2, and PEPT1 were not modulated by LPS treatment. When mizoribine (a CNT1/CNT2 substrate) and gemcitabin (a CNT1 substrate) were administered as a solution dissolved in bile into the intestinal loop, their absorption rates decreased significantly. In contrast, the absorption rate of ribavirin (a CNT2 substrate) remained unchanged. In conclusion, LPS treatment exerted no significant effect on the expression of CNT1 and CNT2 in the intestine. Bile was found to suppress the CNT1-mediated intestinal absorption of mizoribine and gemcitabin. The increased oral bioavailability of mizoribine in LPS-treated rats could be ascribed to the less amount of bile or bile acids in the intestine under cholestatic state of rats.
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PMID:Modulation in concentrative nucleoside transporters-mediated intestinal absorption of mizoribine, an immunosuppressive agent, in lipopolysaccharide-treated rats. 2155 52