乙烷硒啉对犬的长期毒性试验研究  

Study on the long - term toxicity of Ethaselen in dogs

作　　者：林飞[1] 周立娜[2] 吕廉[1] 梁怿[1] 

机构地区：[1]中国药品生物制品检定所,北京100050 [2]中国医科大学

出　　处：《实用肿瘤学杂志》2009年第1期7-10,共4页Practical Oncology Journal

基　　金：国家自然科学基金面上项目（30472036）

摘　　要：目的研究乙烷硒啉连续给药后对犬的毒性反应及其严重程度。方法采用纯种Beagle犬，受试物共分成3个给药组（600mg／kg、200mg／kg和67mg／kg）和1个溶剂对照组，连续口服给药12周，停药后再观察4周，进行一般症状观察、血象、生化、心电图、尿液、骨髓象、眼睛、脏器解剖，脏器系数和组织病理学等检查。结果给药12周高剂量组个别犬在摄食过快时出现呕吐，粪便颜色变浅；谷丙转氨酶和谷草转氨酶增高，葡萄糖降低；肝脏、脾脏和肾脏脏器系数值升高；存在肝细胞脂肪性变和前列腺腺瘤样型肥大的组织病理学变化。停药恢复期基本恢复正常数值。结论乙烷硒啉在相当于临床人拟用量42倍下，连续口服给药后犬仅出现轻度消化道刺激症状，肝功能异常和血糖值降低；轻一中度肝脏、脾脏和肾脏的肿大；轻度一中度的脂肪肝和前列腺腺瘤样型肥大；毒性反应主要集中在消化道，重点在肝脏。犬用药的无明显毒性反应剂量为67mg／kg。Objective To study the toxic effects and severity of ethaselen on beagle dogs. Methods The dosage of ethaselen ,600 mg/kg,200 mg/kg and 67 mg/kg were administered to three groups of beagle dogs separately. Control group was treated with solvent. The drug was given passes through the mouth for 12 successive weeks and 4 observing weeks. Then hematology, blood chemistry, electrocardiogram, urine, marrow, eyes, viscera dissecting,internal organs coefficient and histopathology were examined. Results After 12 weeks treatment,some dogs given high dosage of ethaselen showed symptoms of vomit, slight loss of feces eolour, ALT and AST increase, glucose decline, the coefficient increase of liver, spleen and kidney and histopathology change of liver steatosis and adenomatoid prostate hypertrophy. All the changes basically disappeared after the drug withdrawal. Conclusions With equivalent to 42 times of clinic dosage of ethaselen,beagle dogs showed lightly symptoms such as alimentary tract stimulation,abnormal liver function,glucose level decline, the enlargement of liver ,spleen and kidney ,liver steatosis and adenomatoid prostate hypertrophy. There were toxic effects on alimentary tract, especially on liver. There were no apparently toxic effects to the beagle dogs at the dosage of 67 mg/kg .

关 键 词：乙烷硒啉 BEAGLE犬 长期毒性 消化道刺激 肝功能 

分 类 号：R965.3[医药卫生—药理学]