Inhibition of 20-hydroxyeicosatetraenoic acid (20-HETE) glucuronidation by non-steroidal anti-inflammatory drugs in human liver microsomes and recombinant UDP-glucuronosyltransferase enzymes
| Autor: | Yazun Jarrar, Jae-Gook Shin, Dong-Hyun Kim, Su-Jun Lee |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male Naproxen Mefenamic acid Pharmacogenomic Variants Clinical Biochemistry Glucuronidation 030209 endocrinology & metabolism Pharmacology Polymorphism Single Nucleotide 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship 0302 clinical medicine Diclofenac Glucuronides Hydroxyeicosatetraenoic Acids Republic of Korea medicine Humans Glucuronosyltransferase Rofecoxib 030109 nutrition & dietetics Chemistry Anti-Inflammatory Agents Non-Steroidal Cell Biology Middle Aged UGT2B7 Meloxicam UDP-Glucuronosyltransferase 1A9 Microsomes Liver lipids (amino acids peptides and proteins) Arachidonic acid Female medicine.drug |
| Zdroj: | Prostaglandins, leukotrienes, and essential fatty acids. 153 |
| ISSN: | 1532-2823 |
| Popis: | 20-hydroxyeicosatetraenoic acid (20-HETE) is an arachidonic acid metabolite which is known to increase platelet aggregation and cardiovascular risk. In this study, nine non-steroidal anti-inflammatory drugs (NSAIDs) selected by chemical structures were screened to determine their effects on the glucuronidation of 20-HETE using human liver microsomes (HLMs). Then, the combined effects of the selected NSAID and genetic polymorphisms in UDP-glucuronosyltransferase (UGT) were investigated. Among the tested NSAIDs, diclofenac was the strongest inhibitor of 20-HETE glucuronidation with an IC50 value of 3.5 μM. Celecoxib, naproxen, mefenamic acid, ibuprofen, and indomethacin showed modest inhibition with IC50 values of 77, 91, 190, 208, and 220 μM, respectively, while acetylsalicylic acid, rofecoxib, and meloxicam did not inhibit 20-HETE glucuronidation. Glucuronidation of 20-HETE by UGT2B7 and UGT1A9 recombinant enzymes was significantly inhibited by indomethacin, mefanemic acid, diclofenac, ibuprofen, naproxen, and celecoxib (P |
| Databáze: | OpenAIRE |
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