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A Study on Protective Effect of Vitamin A against Antitumour Drug-Induced Damage to Small Intestine

维生素A对抗肿瘤药物所致小肠损伤的保护作用研究

基本信息

批准号：
03671067
负责人：
HORIE Toshiharu
金额：
$ 1.34万
依托单位：
Tokyo College of Pharmacy
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03671067/
关键词：
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

项目摘要

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.

我们发现维生素A保护小肠免受甲氨蝶呤（MTX）引起的损伤。本研究以维生素A在肿瘤化疗中的临床应用为目的，从以下几个方面进行了研究：(1)维生素A对mtx诱导的肠道损伤的保护机制(2)维生素A对肠道营养物质吸收的改善(3)维生素A对mtx抗肿瘤活性的影响。体外培养的IEC-6细胞未发现维生素A的保护机制。MTX处理大鼠小肠隐窝细胞被破坏，而MTX和维生素A处理大鼠小肠隐窝细胞未受影响。这表明维生素A对隐窝细胞起作用。MTX可降低大鼠小肠对d -葡萄糖、d -木糖和l -亮氨酸等营养物质的吸收，而维生素A与MTX共给药对这些营养物质的吸收没有影响。因此，维生素A被发现可以改善mtx引起的吸收不良。维生素A对培养的L1210小鼠白血病细胞MTX的抗肿瘤活性没有影响。此外，维生素A的联合给药不会干扰接种了L1210白血病细胞和180肉瘤细胞的小鼠的MTX治疗。因此，维生素A被证明可以保护小肠免受MTX诱导的损伤，而不会干扰MTX的抗肿瘤活性。这表明维生素A在MTX治疗中是一种有用的生化调节剂。