Nishisaki H, Sakamoto C, Konda Y, Nakano O, Matozaki T, Matsuda K, Wada K, Nagao M, Kasuga M
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Gastroenterol Jpn. 1991 Feb;26(1):14-9. doi: 10.1007/BF02779503.
To clarify the mechanism by which the administration of anti-tumor drugs, antibiotics or hypoglycemic agents causes gastric mucosal injury, the effects of these drugs on phosphatidylcholine synthesis in isolated guinea pig gastric glands were examined in vitro. Anti-tumor drugs such as tegafur, cyclophosphamide, and mitomycin C decreased [3H]choline incorporation into phosphatidylcholine. Furthermore, tegafur at 0.4 mg/ml decreased [3H]choline incorporation in the glands that had been pulsed with [3H]choline incorporation, suggesting that tegafur exerts its effect by inhibiting late step of phosphatidylcholine synthesis in the stomach. On the other hand, cefaclor and glibenclamide had no effect on [3H]choline incorporation. Geranylgeranylacetone, an anti-ulcer drug partially restored tegafur-induced reduction of [3H]choline incorporation into phosphatidylcholine. These results suggest that the anti-tumor drug-induced gastric mucosal injury may be due to drug-induced decrease in phosphatidylcholine synthesis, which the restoration of phosphatidylcholine synthesis by geranylgeranylacetone may explain its anti-ulcer action on drug-induced gastric mucosal lesions in vivo.
为阐明给予抗肿瘤药物、抗生素或降糖药导致胃黏膜损伤的机制，体外研究了这些药物对分离的豚鼠胃腺中磷脂酰胆碱合成的影响。替加氟、环磷酰胺和丝裂霉素C等抗肿瘤药物减少了[3H]胆碱掺入磷脂酰胆碱。此外，0.4mg/ml的替加氟降低了已用[3H]胆碱掺入脉冲处理的腺体中的[3H]胆碱掺入，这表明替加氟通过抑制胃中磷脂酰胆碱合成的后期步骤发挥作用。另一方面，头孢克洛和格列本脲对[3H]胆碱掺入没有影响。抗溃疡药香叶基香叶基丙酮部分恢复了替加氟诱导的[3H]胆碱掺入磷脂酰胆碱的减少。这些结果表明，抗肿瘤药物诱导的胃黏膜损伤可能是由于药物诱导的磷脂酰胆碱合成减少，而香叶基香叶基丙酮恢复磷脂酰胆碱合成可能解释了其在体内对药物诱导的胃黏膜损伤的抗溃疡作用。
