Tissue-specific regulation of expression and activity of P-glycoprotein in adjuvant arthritis rats
| Autor: | Hisako Fujimura, Toshiyuki Kume, Meguru Achira, Ryuichi Totsuka |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Pharmaceutical Science Arthritis Animal Population Groups Pharmacokinetics In vivo Internal medicine Blood plasma Gene expression Medicine Animals Bile Doxorubicin ATP Binding Cassette Transporter Subfamily B Member 1 Intestinal Mucosa Chromatography High Pressure Liquid P-glycoprotein biology business.industry Blood Proteins medicine.disease Arthritis Experimental Rats Intestines Endocrinology Liver Organ Specificity Rats Inbred Lew Rheumatoid arthritis Area Under Curve Injections Intravenous biology.protein Female business medicine.drug Half-Life Protein Binding |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 16(1-2) |
| ISSN: | 0928-0987 |
| Popis: | Cyclosporine A and steroids are effective against rheumatoid arthritis and also known as substrates of P-glycoprotein (P-gp). We investigated the effect of arthritis on the hepatic and intestinal P-gp activity in rats, and substantiated the expression level of the hepatic P-gp. Doxorubicin was used as a P-gp substrate. Cumulative biliary excretion and intestinal exsorption of doxorubicin following intravenous administration were compared between adjuvant arthritis (AA) and normal rats. Intestinal P-gp activity was also investigated by intestinal everted sac method, and hepatic P-gp was detected by FITC-labeled antibody and visualized using a confocal laser microscope system. Biliary clearance of doxorubicin in AA rats was significantly decreased from that in normal rats. The expression level of the hepatic P-gp in AA rats was very low compared to normal rats, indicating down-regulation. Intestinal exsorption clearance was not different between AA and normal rats. Permeability of doxorubicin across intestinal everted sac was comparable between AA and normal rats, corresponding to in vivo study. In AA rats, hepatic P-gp activity was decreased due to the reduction of expression level, but intestinal P-gp activity was not changed. Different regulation systems may be involved in liver and intestine. |
| Databáze: | OpenAIRE |
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