Slott V L, Hales B F
Toxicol Appl Pharmacol. 1986 Jan;82(1):80-6. doi: 10.1016/0041-008x(86)90440-0.
Certain deleterious effects of cyclophosphamide, for example urotoxicity, can be prevented by the administration of thiol compounds such as 2-mercaptoethane sulfonate (MESNA) without altering the therapeutic efficacy of cyclophosphamide. To evaluate the effect of MESNA on the teratogenicity of cyclophosphamide, pregnant Sprague-Dawley rats were divided into nine treatment groups. Individual groups were administered 0.9% NaCl or cyclophosphamide (10 or 15 mg/kg) alone or in combination with MESNA at one of two doses (5 or 30 mg/kg) on Day 13 of gestation. The fetuses were examined for malformations on Day 20 of gestation. Cyclophosphamide alone produced malformations in 50% (10 mg/kg) or 100% (15 mg/kg) of the fetuses. The abnormalities observed were hydrocephaly, hind- and forelimb defects, open eyes, cleft palate, edema, micrognathia, omphalocele, and various skeletal defects. MESNA alone did not induce a significant number of fetal malformations compared to control. The low dose of MESNA had no significant effect on the total incidence of external malformations produced by either dose of cyclophosphamide. The high dose of MESNA significantly reduced the total number of externally abnormal fetuses and fetuses with skeletal defects produced by both 10 and 15 mg/kg of cyclophosphamide. This protection, although statistically significant (p less than or equal to 0.05), is probably not extensive enough for MESNA to be considered effective in protecting pregnant women from the teratogenic effects of cyclophosphamide chemotherapy.
环磷酰胺的某些有害作用，比如尿路毒性，可以通过给予硫醇化合物如2-巯基乙烷磺酸盐（美司钠）来预防，而不改变环磷酰胺的治疗效果。为了评估美司钠对环磷酰胺致畸性的影响，将怀孕的斯普拉格-道利大鼠分为九个治疗组。在妊娠第13天，各单独组分别给予0.9%氯化钠或单独给予环磷酰胺（10或15mg/kg），或者与两种剂量（5或30mg/kg）之一的美司钠联合给药。在妊娠第20天检查胎儿是否有畸形。单独使用环磷酰胺时，50%（10mg/kg）或100%（15mg/kg）的胎儿出现畸形。观察到的异常有脑积水、后肢和前肢缺陷、睁眼、腭裂、水肿、小颌畸形、脐膨出以及各种骨骼缺陷。与对照组相比，单独使用美司钠并未诱导大量胎儿畸形。低剂量的美司钠对两种剂量环磷酰胺所产生的外部畸形总发生率均无显著影响。高剂量的美司钠显著降低了由10mg/kg和15mg/kg环磷酰胺所产生的外部异常胎儿及有骨骼缺陷胎儿的总数。尽管这种保护在统计学上有显著意义（p小于或等于0.05），但可能还不足以广泛到使美司钠被认为能有效保护孕妇免受环磷酰胺化疗的致畸作用。
