Simulated Microgravity Altered the Metabolism of Loureirin B and the Expression of Major Cytochrome P450 in Liver of Rats
Loureirin B (LB) is the marker compound of dragon blood (DB), which exhibits great potentials in protecting astronauts’ health against radiation and simulated microgravity (SM). Pharmacokinetics of LB is reported to be significantly altered by SM. Here, we investigated key metabolic features of LB i...
| Main Authors: | , , , , , |
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| Formato: | Artigo |
| Idioma: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Acceso en liña: | https://www.frontiersin.org/article/10.3389/fphar.2018.01130/full |
| _version_ | 1831841606485934080 |
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| author | Bo Chen Jingjing Guo Shibo Wang Liting Kang Yulin Deng Yujuan Li |
| author_facet | Bo Chen Jingjing Guo Shibo Wang Liting Kang Yulin Deng Yujuan Li |
| author_sort | Bo Chen |
| collection | DOAJ |
| description | Loureirin B (LB) is the marker compound of dragon blood (DB), which exhibits great potentials in protecting astronauts’ health against radiation and simulated microgravity (SM). Pharmacokinetics of LB is reported to be significantly altered by SM. Here, we investigated key metabolic features of LB in rat liver microsome (RLM) and the effects of SM on LB metabolism as well as on expression of major hepatic cytochrome P450 (CYP450) isoforms. Ten metabolites were tentatively identified based on fragmentation pathways using LC-MS/MS method and elimination kinetics of LB followed a typical Michaelis–Menten equation (Vmax was 1.32 μg/min/mg and Km was 13.33 μg/mL). CYP1A2, CYP2C11, CYP2D1, and CYP3A2 were involved in the metabolism of LB and the relative strength was: CYP3A2 > CYP2C11 > CYP2D1 > CYP1A2. Comparative studies suggested that elimination of LB in RLM was remarkably increased by 3-day and 14-day SM, and the generation of identified metabolites was affected as well. Additionally, 3-day and 14-day SM showed obvious regulatory effects on the expression of major CYP450 isoforms, which might contribute to the increased elimination of LB. The data provided supports for the application of DB as a protective agent and the reasonable use of current medications metabolized by hepatic CYP450 in space missions. |
| first_indexed | 2024-12-23T06:31:45Z |
| format | Article |
| id | doaj.art-f872eaa1f3aa46cd901b7d76c3a29ef2 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-23T06:31:45Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-f872eaa1f3aa46cd901b7d76c3a29ef22022-12-21T17:56:54ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-10-01910.3389/fphar.2018.01130413032Simulated Microgravity Altered the Metabolism of Loureirin B and the Expression of Major Cytochrome P450 in Liver of RatsBo ChenJingjing GuoShibo WangLiting KangYulin DengYujuan LiLoureirin B (LB) is the marker compound of dragon blood (DB), which exhibits great potentials in protecting astronauts’ health against radiation and simulated microgravity (SM). Pharmacokinetics of LB is reported to be significantly altered by SM. Here, we investigated key metabolic features of LB in rat liver microsome (RLM) and the effects of SM on LB metabolism as well as on expression of major hepatic cytochrome P450 (CYP450) isoforms. Ten metabolites were tentatively identified based on fragmentation pathways using LC-MS/MS method and elimination kinetics of LB followed a typical Michaelis–Menten equation (Vmax was 1.32 μg/min/mg and Km was 13.33 μg/mL). CYP1A2, CYP2C11, CYP2D1, and CYP3A2 were involved in the metabolism of LB and the relative strength was: CYP3A2 > CYP2C11 > CYP2D1 > CYP1A2. Comparative studies suggested that elimination of LB in RLM was remarkably increased by 3-day and 14-day SM, and the generation of identified metabolites was affected as well. Additionally, 3-day and 14-day SM showed obvious regulatory effects on the expression of major CYP450 isoforms, which might contribute to the increased elimination of LB. The data provided supports for the application of DB as a protective agent and the reasonable use of current medications metabolized by hepatic CYP450 in space missions.https://www.frontiersin.org/article/10.3389/fphar.2018.01130/fullsimulated microgravitydragon bloodloureirin Bliver microsomehepatic cytochrome P450drug metabolism |
| spellingShingle | Bo Chen Jingjing Guo Shibo Wang Liting Kang Yulin Deng Yujuan Li Simulated Microgravity Altered the Metabolism of Loureirin B and the Expression of Major Cytochrome P450 in Liver of Rats Frontiers in Pharmacology simulated microgravity dragon blood loureirin B liver microsome hepatic cytochrome P450 drug metabolism |
| title | Simulated Microgravity Altered the Metabolism of Loureirin B and the Expression of Major Cytochrome P450 in Liver of Rats |
| title_full | Simulated Microgravity Altered the Metabolism of Loureirin B and the Expression of Major Cytochrome P450 in Liver of Rats |
| title_fullStr | Simulated Microgravity Altered the Metabolism of Loureirin B and the Expression of Major Cytochrome P450 in Liver of Rats |
| title_full_unstemmed | Simulated Microgravity Altered the Metabolism of Loureirin B and the Expression of Major Cytochrome P450 in Liver of Rats |
| title_short | Simulated Microgravity Altered the Metabolism of Loureirin B and the Expression of Major Cytochrome P450 in Liver of Rats |
| title_sort | simulated microgravity altered the metabolism of loureirin b and the expression of major cytochrome p450 in liver of rats |
| topic | simulated microgravity dragon blood loureirin B liver microsome hepatic cytochrome P450 drug metabolism |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.01130/full |
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