2021 Fiscal Year Final Research Report
Evaluation of impact of cyclooxygenase-2 inhibitors on cisplatin-induced nephrotoxicity
| Project/Area Number |
19K16437
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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 | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | シスプラチン / 腎障害 / 非ステロイド性消炎鎮痛薬 / セレコキシブ |
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| Outline of Final Research Achievements |
Non-steroidal anti-inflammatory drugs (NSAIDs) are suggested as a risk factor for cisplatin-induced nephrotoxicity (CIN). In this research, we have minutely evaluated the influence of NSAIDs, particularly inhibition manner of cyclooxygenase, on CIN development.
First, we assessed the impact of NSAIDs co-administration on CIN development using meta-analysis, suggesting that NSAIDs co-administration can worsen CIN. Second, we assessed the influence of each NSAIDs on CDDP-induced cytotoxicity in vivo and in vitro, revealing that celecoxib significantly attenuated and flurbiprofen markedly enhanced renal toxicity by CDDP. In addition, celecoxib attenuated cytotoxicity by reducing oxidative stress and increasing autophagy activation.
In conclusion, we have evaluated NSAIDs influence on CIN, and revealed that celecoxib attenuates CIN by regulating oxidative stress and autophagy activation.
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| Free Research Field |
医療薬学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果よりセレコキシブ特有のCIN予防・軽減作用が示された．本研究はCINマネジメントの観点からCDDPと併用可能なNSAIDsを細分化により探索したものであり，その新規性から学術的意義及び社会的意義は大きいと思われる．さらに，我々のグループはNSAIDsがCDDPの抗腫瘍効果に与える影響も検討しており，その結果も踏まえCDDP投与時のNSAIDsの適正使用に貢献すべくさらなる検討を継続したい．
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