Damasceno Débora Cristina, Volpato Gustavo Tadeu, Person Osmar Clayton, Yoshida Alessandra, Rudge Marilza Vieira Cunha, Calderon Iracema de Mattos Paranhos
Faculdade Estadual de Medicina de Marília, São Paulo, Brasil.
Rev Assoc Med Bras (1992). 2002 Oct-Dec;48(4):312-6. doi: 10.1590/s0104-42302002000400036. Epub 2003 Jan 28.
The aim of this paper was to perform a randomized, controlled and blinded study to investigate if a therapeutic dose of acetylsalicylic acid (ASA), taken by pregnant women, may also cause embryotoxic or congenital abnormalities on experimental animal.
Females were confirmed to have mated by observations of sperm in a vaginal smear. The day on which spermatozoa were found in the vaginal smear was considered as day 1 of gestation (GD1). After randomization, mated females were assigned to experimental groups and individually caged, were given 50 mg/kg/day of acetylsalicylic acid, by needle gavage once daily, during two different periods of pregnancy. One group of dams (n=11) received aspirin from day 1 to 4 of pregnancy (before embryonic implantation) for evaluation of the blastocysts, and another group received aspirin from day 6 to 15 of pregnancy (organogenic period) for fetal evaluation. Control groups (n=12) received distilled water in same volume and during same periods as their respective experimental groups.
The treatment of the dams with ASA, according to minimal therapeutic dose used for humans, did not cause embryotoxic or major malformations on experimental animal but was responsible for rate increased of fetuses presenting ureteric dilatation. After analysis of the data, it appears that, although direct conclusive evidence of adverse effects in humans is lacking, a potential hazard dose exists and thus the indiscriminate use of acetylsalicylic acid (aspirin) is contraindicated.
本文的目的是进行一项随机、对照和双盲研究，以调查孕妇服用治疗剂量的乙酰水杨酸（ASA）是否也会对实验动物造成胚胎毒性或先天性异常。
通过观察阴道涂片上的精子确认雌性已交配。在阴道涂片中发现精子的当天被视为妊娠第1天（GD1）。随机分组后，将已交配的雌性分配到实验组并单独关笼，在妊娠的两个不同阶段，每天通过针头灌胃给予50毫克/千克/天的乙酰水杨酸。一组母鼠（n = 11）在妊娠第1天至第4天（胚胎着床前）接受阿司匹林以评估囊胚，另一组在妊娠第6天至第15天（器官形成期）接受阿司匹林以评估胎儿。对照组（n = 12）在相同时间段内接受与各自实验组相同体积的蒸馏水。
根据用于人类的最小治疗剂量用ASA处理母鼠，并未对实验动物造成胚胎毒性或严重畸形，但导致出现输尿管扩张的胎儿比例增加。数据分析后发现，尽管缺乏关于对人类产生不良影响的直接确凿证据，但存在潜在的危险剂量，因此禁忌随意使用乙酰水杨酸（阿司匹林）。
