2020 Fiscal Year Final Research Report
Impact of alteration of lipid mediator transporter activity on interindividual variety of development of drug-induced liver injury
| Project/Area Number |
18K14965
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Kindai University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 肝障害 / 脂質メディエーター / PGE2 / トランスポーター / 代謝酵素 |
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| Outline of Final Research Achievements |
Prostaglandin E2, one of the lipid mediators, serves as hepatoprotective factor against liver injury triggered by various causes. The purpose of present study is clarifying the impact of alteration of lipid mediator transporter activity on individual development of drug-induced liver injury that occurred in an idiosyncratic manner. Present results suggest that organic-anion transporting polypeptide (OATP) 2A1 that serves as PGE2 transporter is expressed in endothelial cells and Kupffer cells and its expression level is complexly regulated dependent on the types of liver injury. In addition to OATP2A1, moreover, it is revealed that hepatic 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a PGE2 inactivation enzyme, has a great impact on the regulation of hepatic PGE2 amount under liver injury conditions.
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| Free Research Field |
薬物動態学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、脂質メディエーターの動態変動を薬物誘発性肝障害の発症機序の一つとして新たに提言するものである。今回の検討では、OATP2A1の肝臓における発現局在と肝障害に伴う発現変動を明らかにしたことに加え、15-PGDHが肝PGE2量の調節に重要であることを示した。これまでの薬物誘発性肝障害の発祥機序に関する検討は、薬物の体内動態に着目したものがほとんどであったが、本研究成果により内因性肝保護因子であるPGE2の肝臓における量の調節機構の一端が明らかになったことから、今後は新たにPGE2を含む肝保護因子の動態調節機構の個体差の薬物誘発性肝障害の発症への影響を検討することの重要性が示唆された。
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