摘要
为了了解不同剂量的吡咯喹啉醌二钠(PQQ·Na_(2))对小鼠的急性毒性和大鼠的亚慢性毒性并评估其安全性,研究采用经口急性毒性和亚慢性毒性试验(90 d喂养试验),经口急性毒性试验将60只ICR小鼠随机分为6组(1~6组),每组10只,雌雄各半,进行编号标记及称重,按"1∶K系列稀释法"等容量配制各剂量组所需的受试药物溶液,1~6组吡咯喹啉醌二钠按体重经口给药剂量依次为8 000.00,6 062.87,4 594.79,3 482.20,2 639.02,2 000.00 mg/kg,观察PQQ·Na_(2)急性中毒症状并按寇氏法计算LD50及其95%可信限范围。亚慢性毒性试验选用Wistar大鼠,试验设高(按体重2 000 mg/kg)、中(按体重500 mg/kg)、低(按体重125 mg/kg)3个剂量组和阴性对照组,在第45天和第90天检查大鼠的生理状态、血常规指数、体重及血液生化指标,并进行病理解剖及病理组织学检查。结果表明:小鼠PQQ·Na_(2)经口给药后急性中毒症状主要包括精神沉郁、反应迟钝和死亡前全身抖动的神经症状,计算所得PQQ·Na_(2)对小鼠的急性经口LD_(50)为4 027.82 mg/kg,其LD_(50) 95%可信限为3 447.37~4 706.01 mg/kg,根据WHO对化学物质的毒性评级,PQQ·Na_(2)属于实际低毒物质。亚慢性毒性试验中大鼠各项指标均在正常范围内,各剂量组血常规指标、血液生化指标与阴性对照组相比均差异不显著(P>0.05);剖检及主要脏器病理组织学检查均未发现明显变化。说明PQQ·Na_(2)在125~2 000 mg/kg剂量范围内未发现亚慢性毒性,大鼠的最大无作用剂量为2 000.00 mg/kg。
In order to understand the acute toxicity of different doses of pyrroloquinoline quinone disodium(PQQ·Na_(2)) in mice and its subchronic toxicity in rats and to evaluate its safety, the study used oral acute toxicity and subchronic toxicity(90-day feeding) method. Total of 60 ICR mice were selected and randomly divided into 6 groups(groups 1 to 6), 10 in each group, half of the male and female, numbered, labeled and weighed for oral acute toxicity test. According to the "1∶K serial dilution method", the PQQ·Na_(2) solution required for each group was prepared with equal volume. The oral administration doses of PQQ·Na_(2) for groups 1 to 6 were 8 000.00, 6 062.87, 4 594.79, 3 482.20, 2 639.02, 2 000.00 mg/kg. The symptoms of PQQ·Na_(2) acute poisoning were observed and the LD_(50) was determined according to Karber method and the 95% confidence limit range was calculated. The 90-day feeding subchronic toxicity test selected Wistar rats, and the test set up three dose groups: high(2 000 mg/kg according to body weight), medium(500 mg/kg according to body weight), and low(125 mg/kg according to body weight),and negative control group;the physiological status, blood routine indicators, weight, and blood biochemical indicators of the rats were checked on the 45 th and 90 th days, and pathological anatomy and histopathological examinations were performed. The results showed that the symptoms of acute poisoning of PQQ·Na_(2) mainly included depression, unresponsiveness and nerve shaking before death. The calculated oral LD_(50) of PQQ·Na_(2) was 4 027.82 mg/kg, and the 95% confidence limit was 3 447.37-4 706.01 mg/kg. According to WHO’s toxicity rating of chemical substances, PQQ·Na_(2) belonged to actually low toxic substances. In the subchronic toxicity test, all the indicators of the rats were within the normal range. The blood routine indicators and biochemical indicators of the treatment groups showed no significant difference(P>0.05) when compared with the control group. No obvious changes were found in the anatomy and pathologic examination. The results suggested that no subchronic toxicity was found in the test PQQ·Na_(2) in the dose range of 125-2 000 mg/kg, and the maximum no-observed-effect level of the rat subchronic toxicity test was 2 000.00 mg/kg.
作者
郝福星
张颖
彭凯
贾瑜倩
王志强
HAO Fuxing;ZHANG Ying;PENG Kai;JIA Yuqian;WANG Zhiqiang(Jiangsu Agri-animal Husbandry Vocational College,Taizhou 225300,China;Fujian Youbaifu Biological Technology Co.,Ltd.,Fuzhou 350000,China;Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses,College of Veterinary Medicine,Yangzhou University,Yangzhou 225009,China)
出处
《黑龙江畜牧兽医》
CAS
北大核心
2021年第20期117-122,157,158,共8页
Heilongjiang Animal Science And veterinary Medicine
基金
江苏农牧科技职业学院项目(NSFPT201828)。
关键词
吡咯喹啉醌二钠
鼠
急性毒性
亚慢性毒性
氧化还原酶辅酶
pyrroloquinoline quinone disodium
mice
acute toxicity
subchronic toxicity
oxidoreductase coenzyme
