Allan S G, Smyth J F
Br J Cancer. 1986 Mar;53(3):355-60. doi: 10.1038/bjc.1986.59.
Cis-platinum causes profound gastrointestinal symptoms in patients and these may persist for many days after drug administration. Gut mucosal toxicity may be a factor in the pathogenesis of such prolonged nausea, vomiting and anorexia. The effects of cis-platinum on mouse ileal mucosal architecture, villus epithelial cell influx and disaccharidase activity are described in comparison with dhe effects of two platinum analogues, CBDCA and CHIP. In addition the effect of dexamethasone, a useful drug in the palliation of cis-platinum-induced emesis, in combination with cis-platinum is described. Cis-platinum, CBDCA and CHIP cause profound reduction in crypt cell production rate (CCPR) and thus villus epithelial cell influx within hours of administration leading to villus stunting and diminished function. CBDCA showed the least profound effect with early rebound in CCPR by day 3. Cis-platinum and CHIP were roughly equitoxic to ileal crypts with rebound in CCPR being delayed until day 7. Similarly, CBDCA caused least reduction in disaccharidase activity with cis-platinum and CHIP being equitoxic. The addition of dexamethasone had no protective effect on the effects of cis-platinum on murine ileal mucosa and mice given the combination chronically had no weight gain over 18 weeks, their weight paralleling those receiving cis-platinum alone. The platinate compounds have differing degrees of intestinal mucosal toxicity but no direct inference can be drawn in respect to the clinical situation where CBDCA causes less gastrointestinal symptomatology than CHIP but where both cause less than cis-platinum. Dexamethasone does not act by mucosal protection to provide its useful effects in prolonged cis-platinum-induced gastrointestinal symptoms.
顺铂会使患者出现严重的胃肠道症状，且这些症状在给药后可能会持续多日。肠道黏膜毒性可能是导致这种长期恶心、呕吐和厌食的发病机制中的一个因素。本文描述了顺铂对小鼠回肠黏膜结构、绒毛上皮细胞内流和双糖酶活性的影响，并与两种铂类似物卡铂（CBDCA）和异丙铂（CHIP）的影响进行了比较。此外，还描述了地塞米松（一种缓解顺铂所致呕吐的有效药物）与顺铂联合使用的效果。顺铂、卡铂和异丙铂在给药数小时内会使隐窝细胞产生率（CCPR）大幅降低，从而导致绒毛上皮细胞内流减少，进而引起绒毛发育不良和功能减退。卡铂的影响最小，在第3天时CCPR出现早期反弹。顺铂和异丙铂对回肠隐窝的毒性大致相当，CCPR的反弹延迟至第7天。同样，卡铂对双糖酶活性的降低作用最小，顺铂和异丙铂的毒性相当。添加地塞米松对顺铂对小鼠回肠黏膜的影响没有保护作用，长期给予联合用药的小鼠在18周内体重没有增加，其体重与单独接受顺铂治疗的小鼠相当。铂酸盐化合物具有不同程度的肠道黏膜毒性，但对于卡铂引起的胃肠道症状比异丙铂少，且两者都比顺铂少的临床情况，无法直接得出结论。地塞米松并非通过黏膜保护作用来缓解顺铂所致的长期胃肠道症状。
