title: Albumin's Influence on Carprofen Enantiomers-Hymecromone Interaction.
abstract: Hymecromone is an important coumarin drug, and carprofen is one of the most important nonsteroidal antiinflammatory drugs (NSAIDs). The present study aims to determine the influence of bovine serum albumin (BSA) on the carprofen-hymecromone interaction. The inhibition of carprofen enantiomers on the UDP-glucuronosyltransferase (UGT) 2B7-catalyzed glucuronidation of hymecromone was investigated in the UGTs incubation system with and without BSA. The inhibition capability of increased by 20% (P < 0.001) of (R)-carprofen after the addition of 0.5% BSA in the incubation mixture. In contrast, no significant difference was observed for the inhibition of (S)-carprofen on UGT2B7 activity in the absence or presence of 0.5% BSA in the incubation system. The Lineweaver-Burk plot showed that the intersection point was located in the vertical axis, indicating the competitive inhibition of (R)-carprofen on UGT2B7 in the incubation system with BSA, which is consistent with the inhibition kinetic type of (R)-carprofen on UGT2B7 in the incubation system without BSA. Furthermore, the second plot using the slopes from the Lineweaver-Burk versus the concentrations of (R)-carprofen showed that the fitting equation was y=39.997x+50. Using this equation, the inhibition kinetic parameter was calculated to be 1.3 μM. For (S)-carprofen, the intersection point was located in the horizontal axis in the Lineweaver-Burk plot for the incubation system with BSA, indicating the noncompetitive inhibition of (S)-carprofen on the activity of UGT2B7. The fitting plot of the second plot was y=24.6x+180, and the inhibition kinetic parameter was 7.3 μM. In conclusion, the present study gives a short summary of BSA's influence on the carprofen enantiomers-hymecromone interaction, which will guide the clinical application of carprofen and hymecromone.
authors.affiliation: Department of Orthopaedic Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Orthopaedic Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Youshui
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Orthopaedic Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Dang
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Zubin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Orthopaedic Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Kunzheng
authors.initials: K
authors.lastname: Wang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology; D055162:Biocatalysis; D002227:Carbazoles / Q000737:chemistry* / Q000494:pharmacology; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000737:chemistry* / Q000378:metabolism; D006923:Hymecromone / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D003374:Coumarins; D012710:Serum Albumin, Bovine; D006923:Hymecromone; C030123:coumarin; D014453:Glucuronosyltransferase; C007005:carprofen
keywords: bovine serum albumin; carprofen; enantiomers; hymecromone