| Project/Area Number |
03671067
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo College of Pharmacy |
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Principal Investigator |
HORIE Toshiharu Tokyo College of Pharmacy, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (90120154)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Masahiro Science University of Tokyo, Faculty of Pharmaceutical Sciences, Profesor, 薬学部, 教授 (20012669)
AWAZU Shoji Tokyo College of Pharmacy, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60012621)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1992: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1991: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | vitamin A / methotrexate / D-glucose / intestinal damage / intestinal absorption / L1210 murine leukemia cell / crypt cell / cell culture / マウス肉腫細胞ザルコーマ180 / 小腸粘膜 / 抗癌作用 / 小腸培養細胞IEC-6 / L-ロイシン / メトトレキサ-ト / Dーグルコ-ス |
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| Research Abstract |
We found that vitamin A protected the small intestine from methotrexate (MTX)-induced damage. In this study, with an intention of clinical application of vitamin A to cancer chemotherapy, we investigated the follwing subjects : (1)The mechanism of the protection of MTX-induced intestinal damage by vitamin A (2)The improvement of intestinal absorption of nutrients by vitamin A (3)Effect of vitamin A on the antitumour activity of MTX.
1.The in vitro study on cultured IEC-6 cells did not reveal the protective mechanism of vitamin A.The crypt cells of small intestine of rats treated with MTX were found to be damaged, but the cells of rats treated with MTX and vitamin A were unaffected. This suggests that vitamin A acts on the crypt cells.
2.The administration of MTX to rats decreased the small intestinal absorption of nutrients such as D-glucose, D-xylose and L-leucine, but the coadministration of vitamin A with MTX did not affect the absorption of the nutrients. Thus, vitamin A was found to improve the malabsorption induced by MTX.
3.Vitamin A did not affect the antitumor activity of MTX in L1210 murine leukemia cells in culture. Further, coadministration of vitamin A did not disturb the MTX treatment of mice innoculated with L1210 leukemia cells and sarcoma 180 cells. Thus, vitamin A was shown to protect the small intestine from the MTX-induced damage without disturbing the antitumor activity of MTX.This indicates that vitamin A is a useful biochemical modulator in MTX treatment.
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