丙烯腈抗雄激素作用的体内筛检实验研究
Screening for anti-androgenic activities of acrylonitrile in viro
-
摘要:目的 研究丙烯腈(acrylonitrile, AN)的抗雄激素作用。方法 采用美国经济合作与发展组织(OECD)推荐的内分泌干扰体内筛检实验方法(Hershberger test), 对雄性去势大鼠皮下注射剂量为0.4 mg/(kgºbw)丙酸睾酮(testosterone propionate, TP), 同时经口灌胃剂量分别为0, 10, 20, 30, 40, 50 mg/(kgºbw)的受试物丙烯腈以及25mg/(kgºbw)的阳性参照物氟他胺(flutamide, FLU), 每天1次, 连续10 d。最后一次给药24 h后, 将大鼠麻醉后取血并处死, 观察受试动物前列腺、精囊腺、阴茎、肛提肌/球体海绵体肌、尿道球腺等附性腺组织(sex accessory tissue, SAT)重量和肝重、肾重等指标。结果 结果丙烯腈各剂量组与阴性对照组AN剂量为0 mg/(kgºbw)相比, SAT重量差异无统计学意义(P > 0.05), 阳性对照组(FLH)与阴性对照组相比, SAT重量差异有统计学意义(P < 0.05)。丙烯腈各剂量组肝、肾重量与阴性对照组差异无统计学意义(P > 0.05), 提示受试动物无明显系统毒性。结论 采用Hershberger体内筛检试验未发现丙烯腈具有抗雄激素作用。Abstract:Objective To investigate the anti-androgenic effect of acrylonitrile(AN)by the Hershberger assay in rats.Methods Acrylonitrile was administered orally at doses of 0, 10, 20, 30, 40 and 50 mg/(kgºbw)to castrated rats for 10 days. 0.4 mg/(kgºbw)testosterone propionate(TP)was also administered by subcutaneous injection after the administration of AN. In some rats, flutamide (FLU)was also administered orally at a dose of 25 mg/(kgºbw)as the reference chemical for(anti-)androgenicity. All rats were killed 24 h after the administration of the last dose. The sex accessory tissue weights, including the weights of prostate, seminal vesicle, penis, LA/BC muscle and Cowper's gland, and the weights of kidney and liver of rats were recorded.Results There were essentially no differences in sex accessory tissue weights between the negative control and any of the AN-treated groups(P > 0.05). The positive control flutamide25 mg/(kgºbw)showed a significant effect in this assay protocol(P < 0.05). There was no excessive systemic toxicity in this assay(P > 0.05).Conclusion AN mayn't have anti-androgenic properties on in vivo screening tests.
下载: