金丝桃苷对Beagle犬的长期毒性研究

Long-term toxicity of hyperoside in Beagle dogs

目的:观察连续灌胃(ig)给予金丝桃苷对Beagle犬的长期毒性反应,以评价其长期用药的安全性。方法:Beagle犬32只,随机分为金丝桃苷低、中、高剂量组(8,65和500 mg·kg-1·d-1)和空白对照组(给予1%羧甲基纤维素钠溶液),每组8只,雌雄各半。每天ig给药1次,连续38周(每周日停药1 d),并进行4周恢复性观察。检查金丝桃苷各剂量组Beagle犬的一般状况、体重变化、摄食量、体温、眼科、尿常规、心电图、血液学及血清生化学指标,大体解剖及组织病理学检查。结果:实验期间,没有发现动物死亡或濒死。金丝桃苷各剂量组动物用药期间一般状况良好,体重变化、摄食量、体温、眼科、尿常规、心电图、血液学及血清生化学等各项临床检验未见与药物有关的异常改变。病理学检查可见个别动物有肝脏和肾脏损伤,但在恢复期结束时未见以上毒性,提示毒性反应可逆。结论:金丝桃苷具有较好的安全性,肝脏和肾脏是可能的毒性靶器官,但损害是可逆的,建议临床使用时定期进行肝脏和肾脏功指标监测。

Objective： To investigate the chronic toxicity of hyperoside in Beagle dogs. Methods： Beagle dogs（ n = 32） were randomly divided into four groups（ 8 dogs in each group,4 per sex）. Hyperoside 8,65 and500 mg·kg^- 1·d^- 1 or 1% aqueous carboxymethylcellulose（ control） were administered by gavage for 38 weeks to Beagle dogs（ with subsequent 1 month recovery period）. Mortality,clinical signs,body weight changes,food consumption,temperature,eye examination,electrocardiogram,routine urine test,hematological and biochemical parameters,gross findings,organ weights and histological markers were monitored during dosing and recovery period.Results： In the period of test,no death or articulo mortis was found. No abnormal clinical reactions were found in hyperoside groups compared with control group. Histological examination indicated that liver and kidney were possible toxic target organs,but the damage was reversible. Conclusion： In general,hyperoside has a good safety.Liver and kidney are possible toxic target organs,but the damage is reversible and could return to normal after withdrawal. We suggest that regular liver and kidney function index monitoring may be necessary when hyperoside is clinically used.