A comparison of the expression and metabolizing activities of phase I and II enzymes in freshly isolated human lung parenchymal cells and cryopreserved human hepatocytes
| Autor: | N. Lindsay, Graham Somers, C. Freathy, S. Ho, Martin K. Bayliss, B. M. Lowdon, Gary R. Manchee, Amanda Woodrooffe, A. E. Jones |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Sulfotransferase Glucuronidation Pharmaceutical Science Biology Sulfation Cytochrome P-450 Enzyme System Parenchyma medicine Humans Glucuronosyltransferase Lung Cells Cultured Aged Pharmacology Cryopreservation Epoxide Hydrolases CYP3A4 Cytochrome P450 respiratory system Middle Aged respiratory tract diseases medicine.anatomical_structure Biochemistry Hepatocyte biology.protein Hepatocytes Female Sulfotransferases Drug metabolism |
| Zdroj: | Drug metabolism and disposition: the biological fate of chemicals. 35(10) |
| ISSN: | 0090-9556 |
| Popis: | The pulmonary and hepatic expression and catalytic activities of phase I and II drug-metabolizing enzymes were compared using human lung and liver tissue, and lung parenchymal cells (LPCs) and cryopreserved hepatocytes. Cytochrome P450 gene expression was generally lower in lung than in liver and CYP3A4 expression in lung was negligible. Esterase gene expression was similar in lung and liver. Expression of all sulfotransferase isoforms in lung was similar to or higher than that in liver. Lung tissue expressed low levels of UGT. However, the expression of UGT2A1 in lung was higher than that in liver. There was a range of catalytic activities in LPCs, including cytochrome P450, esterase, and sulfation pathways. Phase I activities were generally less than 10% of those determined in hepatocytes. Rates of ester hydrolysis and sulfation in LPCs were similar to those in hepatocytes. When measurable, glucuronidation in LPCs was present at very low levels, reflecting the gene expression data. The metabolism of salbutamol, formoterol, and budesonide was also investigated. Production of salbutamol-4-O-sulfate and budesonide oleate was observed in LPCs from at least two of three donor preparations studied. Formoterol sulfate and low levels of formoterol glucuronide were detected in one of three donors. In general, drug-metabolizing capability of LPCs is low compared with liver, although some evidence for substantial sulfation and deesterification capacity was observed. Therefore, these data support the use of this cell-based system for the investigation of key routes of xenobiotic metabolism in human lung parenchyma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|