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

我们发现维生素A保护小肠免受甲氨蝶呤（MTX）诱导的损伤。本研究以维生素A在肿瘤化疗中的临床应用为目的，对以下几个方面进行了研究：（1）维生素A对MTX所致肠道损伤的保护机制（2）维生素A对肠道营养吸收的促进作用（3）维生素A对MTX抗肿瘤活性的影响6细胞未揭示维生素A的保护机制。MTX处理的大鼠小肠隐窝细胞受到损伤，而MTX和维生素A处理的大鼠小肠隐窝细胞不受影响。2. 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，但MTX与维生素A合用对这些营养物质的吸收无影响。维生素A对MTX诱导的L1210小鼠白血病细胞的抗肿瘤活性无明显影响。此外，维生素A的共同管理并没有干扰MTX治疗接种L1210白血病细胞和肉瘤180细胞的小鼠。因此，维生素A显示出保护小肠免受MTX诱导的损伤而不干扰MTX的抗肿瘤活性。这表明维生素A是MTX治疗中有用的生化调节剂。

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.