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Decreased urinary secretion of belotecan in folic acid-induced acute renal failure rats due to down-regulation of Oat1 and Bcrp.
- Source :
-
Xenobiotica . Oct2009, Vol. 39 Issue 10, p711-721. 11p. 1 Color Photograph, 1 Diagram, 3 Charts, 4 Graphs. - Publication Year :
- 2009
-
Abstract
- 1. The effects of folic acid-induced acute renal failure on the renal excretion of belotecan were investigated in rats after intravenous administration. 2. Both glomeruli and renal tubules were seriously damaged by folic acid-induced acute renal failure. The renal excretion clearance, CLr, of belotecan was significantly decreased by folic acid-induced acute renal failure. Furthermore, glomerular filtration rate and secretion clearance of the drug were dramatically decreased by folic acid-induced acute renal failure. 3. In vivo renal uptake of belotecan was inhibited by p-aminohippurate, whereas renal excretion was inhibited by GF120918, but not by verapamil and bromosulphalein. This indicates that Oat1/3 and Bcrp are involved in the renal uptake and urinary excretion of belotecan, respectively. 4. Both mRNA and protein levels of Oat1, Oat3 and Bcrp were significantly decreased in folic acid- induced acute renal failure rats. Based on the finding that belotecan is a substrate of OAT1 but not of OAT3, the decrease in CLr of belotecan in folic acid-induced acute renal failure could, therefore, mainly be attributed to the down-regulation of Oat1 and Bcrp, in addition to the decrease in glomerular filtration rate. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00498254
- Volume :
- 39
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Xenobiotica
- Publication Type :
- Academic Journal
- Accession number :
- 44029888
- Full Text :
- https://doi.org/10.1080/00498250903026458