摘要
为评价抗鸡球虫病药物常山口服液的安全性,本试验采用改良寇氏法和剂量递增法对小鼠进行急性毒性试验研究,并通过病理组织学观察来明确常山口服液毒性损伤的主要靶器官。取60只昆明系小鼠,雌雄各半,随机分为6组,1个对照组和5个给药组,给药组分别按1.00、1.40、1.96、2.74和3.84g/kg体重的剂量灌胃给药,连续观察7d,记录小鼠急性毒性反应过程,并运用改良寇氏法公式计算半数致死量（LD50）及LD50的95%可信限。结果显示,小鼠经口灌胃LD50为2.0961g/kg体重,LD50的95%可信限为1.7414~2.5429g/kg体重;剖检可见1.96、2.74和3.84g/kg体重剂量组部分小鼠的肝脏、肾脏出现较严重的水肿、充血和明显的白色坏死灶;病理组织学检查显示小鼠出现急性肝脏损伤,表现为肝细胞退行性改变,病变主要是小叶周边变性、坏死及崩解,而肾脏损伤表现为肾淤血、间质水肿、肾曲小管上皮浊肿和广泛变性,各主要脏器以肝脏损害较为严重,可确定常山口服液损伤的靶器官主要为肝脏。结果表明,常山口服液按常规剂量使用是安全的,临床用于抗球虫病安全性较高,但大剂量、长疗程的用药会出现毒性反应,由于急性毒性试验观察时间较短,故还应结合长期毒性试验的毒性表现及多种检查结果综合分析评价其毒性。
The purpose of this study was to evaluate drug safety of Dichroa febrifugaoral liquid（DFOL）,and the acute toxicity test of DFOL was established in mice based on modified Karber＇s method and dose increasing method,and histopathological examination had been applied to explore the main target organs of its toxic injury.The dosage was determined by preliminary experiment,a total of 60 Kunming mice were selected and divided randomly into one control group and five experimental groups,DFOL was administered by intragastric gavage at five different doses（1.00,1.40,1.96,2.74,3.84g/（kg·BW））,and observed for 7days continuously,the LD50 value and 95% confidence interval of LD50 were determined by the modified Karbers method.It showedthat LD50 was 2.0961 g/（kg · BW）and its 95% confidence interval was 1.7414 to2.5429g/（kg·BW）.The liver and kidney of some mice in 1.96,2.74 and 3.84g/（kg·BW）drug groups appeared severe edema,congestion and white necrotic foci by necropsy.Acute liver injury was found in mice by histopathological examination and the liver cell showed degenerative change,kidney damage showed renal congestion,interstitial edema,renal tubule epithelial cloudy swelling and degeneration.The liver was damaged seriously in the main organ and the main toxic organ of DFOL was liver.The test showed that the toxicity of DFOL was lower and it had high security in a conventional doses for clinical anti-coccidiosis application,however,high dose,long course of medication had toxicity,and the toxicity of DFOL should be analyzed and evaluated combining with long-term toxicity tests and many other inspection results.
出处
《中国畜牧兽医》
CAS
北大核心
2016年第10期2724-2729,共6页
China Animal Husbandry & Veterinary Medicine
基金
中央级公益性科研院所专项资金项目(1610322011004)
横向委托项目(2015-007)
关键词
常山口服液
急性毒性
组织病理
靶器官
Dichroa febrifugaoral liquid（DFOL）
acute toxicity
tissue pathology
target organ
