Es-生物炔丙菊酯原药对大鼠的致畸作用

Es-生物炔丙菊酯(prallethrin)的化学名称是(S)-2-甲基-4-氧代-3-(2-炔丙基).环戊-2-烯基(1R,3R).2,2-二甲基-3-(2-甲基-1-丙烯基)环丙烷羧酸酯,主要用于防治家蝇、蚊虫、虱和蟑螂等家庭害虫,现研究Es-生物炔丙菊酯原药对大鼠的致畸作用,说明其是否具有胚胎毒性和致畸作用,求出其致畸作用的最大无作用剂量(NOAEL),为其安全使用提供依据.     

碳铂对大鼠胚胎毒性与致畸作用的研究

碳铂(卡铂,Carboplatin)是继顺铂之后第二代铂类抗癌新药,它与顺铂有相似的抗癌谱,而消化道和肾毒性明显较低,国内自80年代末广泛用于临床。本文报道它的胚胎毒性和致畸作用。 材料与方法 碳铂,水溶性白色粉末,溶于6％葡萄糖溶液中使用,昆明贵金属研究所杨懿昆和熊惠周等同志合成和提供。动物用Wistar大鼠,体重223±229(X±SD)。方法参照Keller等[1～3]。雌雄2:     

甲基汞对大鼠的行为致畸效应研究

目的探讨妊娠期甲基汞暴露对Wistar大鼠的母体毒性及仔代的行为致畸效应.方法 Wistar孕鼠80只于妊娠第6～9天采用甲基汞0.00、0.01、0.05和2.00mg·kg-1@d-1连续灌胃染毒.分别进行母体毒性、胚胎毒性、仔鼠早期生理发育和神经行为发育指标、仔鼠迷宫和程序控制行为测试、亲仔两代大鼠脑组织形态学观察和单胺类神经递质(去甲肾上腺素、多巴胺、5-羟色胺)的测定.整个实验采用双盲法.结果未观察到明显的母体毒性;3个剂量组胎仔的体重、尾长均低于对照组(P＜0.01);各剂量组仔鼠的体重增长、早期生理及神经行为发育滞后于对照组(P＜0.05);各剂量组仔鼠迷宫错误次数均比对照组多(P＜0.05),具有剂量-效应关系(rs=0.257,P＜0.05);程序控制行为学习成绩比对照组降低(P＜0.05),有剂量-效应关系(rs=-0.727 3,P＜0.01);各剂量组母鼠和仔鼠脑组织均未见形态学改变,但脑组织单胺类神经递质含量均比对照组明显增高(P＜0.05),有剂量-效应关系(s=0.712 4～0.925 7,P＜0.01).结论甲基汞在不引起可观察到母体毒性剂量下,就可产生胚胎毒性,影响仔鼠神经系统的发育,导致神经行为功能的改变.     

汉黄芩素对大鼠致畸敏感期的毒性试验

目的：观察汉黄芩素对大鼠致畸敏感期的毒性反应。方法：将SD大鼠随机分为4组,每组16只,设空白对照组和汉黄芩素40,13．3,4．4mg·kg^-1剂量组,在受孕大鼠致畸敏感期（受孕第6～15d）给药,观察各组孕鼠的毒性情况。结果：汉黄芩素高剂量组孕鼠体重增长缓慢,躯干骨的胸骨数、骶尾椎数,前肢手掌骨的中手骨数、指骨总数和后肢脚掌骨的中足骨数、趾骨总数减少,与空白对照组相比差异也有显著性意义;高、中剂量组胎鼠的头顶骨、侧头骨和后头骨骨化不全数,与空白对照组相比差异有显著性意义（P〈0．01）。结论：未发现汉黄芩素对胎鼠有明显致畸作用。但该药高剂量可使胎鼠骨骼发育迟缓。     

美洛昔康对大鼠致畸敏感期的毒性试验研究

美洛昔康在受孕大鼠致畸敏感期（受孕后第6－15天）给药,剂量分别为7.0,3.5,1.8mg/kg。结果未发现美洛昔康对胎鼠有致畸作用,但该药可使胎鼠体重减轻,吸收胎和死胎增多,骨骼发育迟缓,尤以给予高剂量美洛昔康时明显。     

美洛昔康对大鼠致畸敏感期的毒性试验研究

美洛昔康在受孕大鼠致畸敏感期(受孕后第6～15天)给药,剂量分别为7.0,3.5,1.8 mg/kg.结果未发现美洛昔康对胎鼠有致畸作用,但该药可使胎鼠体重减轻,吸收胎和死胎增多,骨骼发育迟缓,尤以给予高剂量美洛昔康时明显.     

连翘酯苷冻干粉对SD大鼠的致畸作用

目的探讨连翘酯苷冻干粉的对SD大鼠的致畸作用.方法采用大鼠标准致畸试验,孕SD大鼠随机分为4组,每组20只.实验组剂量分别为0.075,0.150,0.3 g·kg-1,对照组给予生理氯化钠溶液.妊娠d 6～15尾静脉注射给药,qd.妊娠d 20处死孕鼠,检查母体妊娠与胎鼠畸形情况.结果各实验组对母鼠增重、胎鼠外观畸形率、内脏畸形率、活胎率、死胎率、吸收胎率、活胎身长、胎盘重和胎鼠体重无显著影响.同时,在各受试剂量作用下对骨骼的发育也无明显影响.结论连翘酯苷冻干粉冻干粉在受试剂量下无明显的母体毒性和致畸作用,也无明显的胚胎毒性和胎儿毒性.     

右旋丙亚胺(ICRF-187)预防蒽环类所致心脏毒性的基础研究

目的：探讨右旋亚丙胺（ＩＣＲＦ－１８７）预防蒽环类所致心脏的药理机制。方法：电子顺磁共振法（ＥＰＲ）、核磁共振法（ＮＭＲ）、质子相关分光术、光镜、电镜、免疫组织化学、生化反应、细胞培养及自发性高血压＊ＳＨＲ）小鼠模型。结果：①ＩＣＲＦ－１８７转换铁－蒽环类复合物中的铁，并与铁络合以抑制自由基的产生；②ＩＣＲＦ－１８７减弱心脏毒性免疫效应细胞（树突状细胞，ＴＨ，ＴＣ淋巴细胞及巨噬细胞）的作用；③ＩＣ     

Teratogenicity of flubendazole in rats

Flubendazole, the p-fluoroderivative of mebendazole, was suspended in deionized water, and administered by gavage once daily to pregnant rats on days 8 through 15 of pregnancy at 0 (control), 2.5, 10, 40 or 160 mg/kg. Fetuses were removed on day 21 of pregnancy by caesarian section, and examined by routine teratological methods. The highest dose (160 mg/kg) was embryocidal and resulted in a significant increase in the fetal resorption rate. There was a dose-dependent decrease in fetal body weights which was significant at 40 mg/kg or more. The 40 and 160 mg/kg doses induced significant fetal (gross, skeletal and internal) malformations. A variety of gross malformations occurred, i.e. encephalocele, cranial meningocele, omphalocele, ectrodactyly, club foot, defects in tail, anal atresia, shortened backbone and Spina bifida occulta. The skeletal malformations mainly affected the vertebrae and ribs. The most frequently observed internal malformation was hydrocephaly, followed by anophthalmia and/or microphthalmia.     

Teratogenicity of di-n-butyltin dichloride in rats

Pregnant rats were given di-n-butyltin dichloride (DBT) by gastric intubation at a dose of 0, 2.5, 5.0, 7.5 or 10.0 mg/kg on days 7-15 of pregnancy. Maternal toxicity occurred in the 7.5 and 10.0 mg/kg groups as evidenced by a significant increase in maternal death and decrease in food consumption and body weight gain. The incidence of fetuses with malformations was roughly proportional to the dose of DBT, and was significantly increased in the 5.0, 7.5 and 10.0 mg/kg groups. Cleft jaw, ankyloglossia, defects of the mandible, fusion of the ribs and deformity of the vertebral column were predominantly found. It is concluded that DBT produced teratogenic effects in the absence of maternal toxicity.     

Teratogenicity study of ethylene glycol in rats

Ethylene glycol was administered in the diet to pregnant Fischer 344 rats on days 6 through 15 of gestation. Target dosage levels were 1.0, 0.2, 0.04, and 0.00 g/kg/day. There was no maternal toxicity, embryotoxicity, or increased incidence of malformations in fetuses from doses dams. Positive control dams received 500 mg/kg of hydroxyurea on gestation day 11 and had fetuses with numerous soft tissue and skeletal malformations. Results are interpreted as preliminary indication of lack of teratogenicity of ethylene glycol.     

Teratogenicity in rats of two dopaminergic agonists

The teratogenic potential of 2 structurally related dopaminergic agonists, BRL 16644 (2-[[3,4-dihydro-2,2-dimethyl-4-[3-(trifluoromethyl)phenyl]-2H- 1-benzopyran-7-yl]oxy]-N,N-dimethyl-Ethanamine: Chemical Abstracts No. 59257-18-0) and BRL 16657 (2-[[3,4-dihydro-2,2-dimethyl-4-[4-(trifluoromethyl)phenyl]-2H- 1-benzopyran-7-yl]oxy]-N,N-dimethyl-Ethanamine: Chemical Abstracts No. 59257-24-8), has been investigated in pregnant Sprague-Dawley rats. These compounds were administered orally from Days 6 to 15 of gestation inclusive at dose levels of 10, 20 and 40 mg/kg/day for BRL 16644 and 10, 20 and 35 mg/kg/day for BRL 16657. At caesarean section on Day 21 of gestation increased post-implantation loss, reduced foetal weights and high incidences of gross abnormalities were found with both compounds at their high dose levels. Maternal toxicity was evident at the intermediate and high dose levels but teratogenic effects extended to the low dose of each compound where treatment was well tolerated by the dams. The maternal effects were thought to be due to the dopamine potentiating properties of BRL 16644 and BRL 16657. When pimozide, a specific dopamine antagonist, was co-administered with BRL 16657 the maternal effects were considerably reduced and, although teratogenicity remained, effects of BRL 16657 on the embryo were extensively modified. This suggests that at least certain of the abnormalities were associated with prolonged dopamine potentiation. Pimozide alone was not teratogenic.     

Teratogenicity and embryotoxicity study of Green S in rats

Daily oral doses of 0 (control), 250, 500 or 1000 mg Green S/kg body weight were given to groups of 30 pregnant rats on days 0–19 of pregnancy. This treatment did not adversely influence maternal body weight, the numbers of implanations, of pre- or post-implantation losses or of live foetuses, the sex ratio or the weight of the litters or foetuses. No definite abnormalities were seen and the only finding in the examination of stained skeletons was a slightly more advanced ossification of the forelimbs of the offspring from females given 500 or 1000 mg Green S/kg/day. More foetuses with mucus in the trachea were found in the treated groups than in the controls but this was not considered to be a teratogenic effect. Thus no embryotoxic or teratogenic effects were detected with doses of up to 1000 mg Green S/kg/day throughout pregnancy.