阿司匹林丁香酚酯的一代繁殖毒性研究

Reproductive Toxicity in Parental Generation of Aspirin Eugenol Ester on Rats

关键词:  阿司匹林丁香酚酯  生殖毒性  发育毒性  繁殖指标

Key words:  aspirin eugenol ester  reproductive toxicity  developmental toxicity  reproductive indexes

摘要:

为了初步评价阿司匹林丁香酚酯（AEE）对亲代大鼠的生殖功能和子代早期发育的影响，将360只Wistar大鼠随机分成6组，分别为受试药物AEE高、中、低剂量组（剂量分别为498.0、124.5和31.1 mg·kg-1·d-1），阿司匹林组（剂量为68.4 mg·kg-1·d-1），丁香酚组（剂量为246.0 mg·kg-1·d-1），空白对照组（给予常规维持饲料）。各实验组均按设定剂量连续给药10周后，测定亲代大鼠主要的脏器系数、繁殖指数和生产指标以及子代（F1）仔鼠的出生指标和生长指标。结果显示，与空白对照组相比，高剂量的AEE影响胎鼠的生长（P<0.05），并且高剂量AEE组大鼠的妊娠率、窝产仔数、出生活仔率和出生存活率都偏低，其中雄性仔鼠比例偏高；阿司匹林组妊娠大鼠和哺乳期胎鼠生长缓慢（P<0.05）；高剂量组AEE亲代大鼠的睾丸和附睾系数偏高（P<0.05），阿司匹林和丁香酚组子代大鼠的附睾系数偏高（P<0.05）。结果表明，在本试验条件下，AEE对大鼠繁殖毒性的最大无损害作用剂量为31.1 mg·kg-1·d-1，对大鼠的最小有损害作用剂量为124.5 mg·kg-1·d-1。

Abstract:

The reproductive and developmental toxicity of aspirin eugenol ester (AEE) in rats were investigated. Parental generation were exposed to AEE at doses of 498.0、124.5 and 31.1 mg·kg-1·d-1 and aspirin at dose of 68.4 mg·kg-1·d-1 and eugenol at dose of 246.0 mg·kg-1·d-1 for 10 weeks before breeding. The weights of main organs and breeding indexes were observed in P and first filial generation (F1). Results showed that the body weights of P and F1 were decreased (P<0.05), and pregnancy rate, litter size, live birth index and viability index on day 4 in high AEE dose group were also lower than those of control group. In addition, high male proportion in sex ratio of F1 was very abnormal. Pregnant rats and weaning index in aspirin group grew slowly (P<0.05). Compared to control group,testis and epididymis indexes of P rats in high dose AEE group were high (P<0.05), and epididymis indexes of F1 rats in aspirin and eugenol groups were also high (P<0.05). Under the experimental condition, AEE had reproductive toxicity in rats. No observed adverse effect level was 31.1 mg·kg-1·d-1. Low observed adverse effect leve was 124.5 mg·kg-1·d-1.