2017 Fiscal Year Final Research Report
Mechanism of cyclophosphamide-induced fatal cardiotoxicity on cardiomyocytes derived from human iPS cells
| Project/Area Number |
16H07088
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Hygiene and public health
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| Research Institution | Kagoshima University |
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Principal Investigator |
MIYAHARA Emiko 鹿児島大学, 医歯学総合研究科, 特任研究員 (20778427)
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| Project Period (FY) |
2016-08-26 – 2018-03-31
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| Keywords | 毒性学 / 抗がん剤 / シクロホスファミド / 心筋障害 / アクロレイン |
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| Outline of Final Research Achievements |
Administration of cyclophosphamide (CY) increased the acrolein-lysine adducts in mice plasma. Aldehyde dehydrogenase 1 (ALDH1) in mice white blood cells were activated by N-acetylcysteine (NAC). And under the active ALDH1, CY was metabolized to carboxyethylphosphoramide mustard, which is noncytotoxic metabolite of CY. Furthermore, vacuole degeneration or eosinophilic generation in the hearts and livers in mice were suppressed by NAC treatment.
In these results indicate that the concentration of acrolein in the blood after administration of CY and ALDH1 activity are important factor on CY-induced cardiotoxicity. Therefore, these factors may contribute to prevent the CY-induced cardiotoxicity.
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| Free Research Field |
毒性学
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