青蒿浸膏对昆明小鼠和Wistar大鼠的急性毒性试验
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摘要
青蒿浸膏为青蒿素提取过程中的初提物,它可以提高动物生长性能和机体免疫力,有抗鸡球虫、杀灭纤毛虫等功效,在畜牧养殖上有广泛的应用前景,然而其毒性大小尚未见报道。本试验采用Bliss法设计,分别对昆明小鼠和Wistar大鼠单次灌胃青蒿浸膏(青蒿素的质量分数为170 g/kg±10 g/kg),测定它对昆明小鼠和Wistar大鼠的半数致死量(LD50)及其95%可信限,分别观察7 d内昆明小鼠和Wistar大鼠的毒性反应和死亡情况,对昆明小鼠和Wistar大鼠分别进行大体解剖和组织病理学检查。结果,各剂量组小鼠均未出现明显的中毒症状,自由活动正常,饮食饮水正常,且无死亡个体;各剂量组雌、雄小鼠的体重也没有显著变化。与小鼠不同,大鼠毒性症状随青蒿浸膏的剂量增加而逐渐加重,4120 mg/kg剂量组仅见自发活动减少;6 460mg/kg和8 080 mg/kg组可见少量个体震颤、强制性-阵挛性抽搐,死亡等症状;10 100 mg/kg剂量组小鼠可见震颤、强制性-阵挛性抽搐、角弓反张、死亡等症状。Wistar大鼠的LD50为7 360 mg/kg,95%的可信限为6 256.38~8 658.82 mg/kg。上述试验结果表明,青蒿浸膏属于无毒物质。
The extract containing artemisinin from Artemisia annua L.can improve the growth performance of animal and immune functions,also resist against chicken coccidiosis and kill ciliate.So these extract have a wide range of application prospects in the animal husbandry industry.However,the toxicity effect of the extract remains unclear.In order to evaluate the toxicity of the extract,using the Bliss method,the LD50 and its 95%confidence of this extract(Artemisinin content:170 mg/kg±10 mg/kg) in Kunming mice and Wistar rat were determined after single oral administration within 7 days.In result,the mice from different dose group did not appear toxic symptoms,even these mice had normal locomotoractivity,feeding and water intake.There was no obvious difference between males and females on weight,after being exposed to this extract.But in Kunming mice,the effects of toxicity in rat were gradually in reased in a dose-dependent manner,in the group of 4 120 mg/kg just reduced locomotor activity,and the 6 460 mg/kg,8 080 mg/kg and 10 100 mg/kg treatment groups with the extract displayed the symptoms of individual tremor,compulsion clonic convul sion and death.The LD50 was 7 360 mg/kg,and the 95% confidence limit was from 6 256.38 to 8 658.82 mg/kg in rat.In summary,the extract from Artemisia annua is nontoxic substance with nontoxicity in Kunming mice and Wistar rat.
The extract containing artemisinin from Artemisia annua L.can improve the growth performance of animal and immune functions,also resist against chicken coccidiosis and kill ciliate.So these extract have a wide range of application prospects in the animal husbandry industry.However,the toxicity effect of the extract remains unclear.In order to evaluate the toxicity of the extract,using the Bliss method,the LD50 and its 95%confidence of this extract(Artemisinin content:170 mg/kg±10 mg/kg) in Kunming mice and Wistar rat were determined after single oral administration within 7 days.In result,the mice from different dose group did not appear toxic symptoms,even these mice had normal locomotoractivity,feeding and water intake.There was no obvious difference between males and females on weight,after being exposed to this extract.But in Kunming mice,the effects of toxicity in rat were gradually in reased in a dose-dependent manner,in the group of 4 120 mg/kg just reduced locomotor activity,and the 6 460 mg/kg,8 080 mg/kg and 10 100 mg/kg treatment groups with the extract displayed the symptoms of individual tremor,compulsion clonic convul sion and death.The LD50 was 7 360 mg/kg,and the 95% confidence limit was from 6 256.38 to 8 658.82 mg/kg in rat.In summary,the extract from Artemisia annua is nontoxic substance with nontoxicity in Kunming mice and Wistar rat.
引文
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[7]席世玲,高玲,赵瑾,等.青蒿素的药理作用及其在畜牧生产中的应用[J].上海畜牧兽医通讯,2009,(06):64-65.XI Shi-ling,GAO Ling,ZHAO Jin,et al.Pharmacological action of artemisinin and its application in animal production[J].Shanghai Journal of Animal Husbandry and Veterinary Medicine,2009,(06):64-65.(in Chinese)
[8]拜彬强,郝力壮,刘书杰,等.青蒿提取物对藏羊瘤胃体外产气发酵特性及甲烷产量的影响[J].江苏农业科学,2015,43(12):227-231.BAI Bin-qiang,HAO Li-zhuang,LIU Shu-jie,et al.Effects of artemisia annua extract on rumen gas production,fermentation characteristics and methane production in Tibetan Sheep[J].Jiangsu Agricultural Sciences,2015,43(12):227-231.(in Chinese)
[9]孙红梅,郝力壮,冯宇哲,等.青蒿提取物对牦牛瘤胃发酵及甲烷产量的影响[J].家畜生态学报,2015,36(08):34-40.SUN Hong-mei,HAO Li-zhuang,FENG Yu-zhe,et al.Effect of artemisinin on rumen fermentation and methane emissions of yak[J].Journal of Domestic Animal Ecology,2015,36(08):34-40.(in Chinese)
[10]《化学药物急性毒性试验技术指导原则》课题研究组.化学药物急性毒性试验技术指导原则[M].北京:中国医药科技出版社,2010:1-15.《Technical guidelines for acute toxicity test of chemical drugs》group of subject study.Technical Guidelines for Acute Toxicity Test of Chemical Drugs[M].Beijing:China Medical Science Press,2010:1-15.(in Chinese)
[11]孟茹,李重阳,俞诗源,等.当归(粗)多糖对麻黄素肝组织损伤的保护作用[J].解剖学报,2015,46(03):379-386.MENG Ru,LI Chong-yang,YU Shi-yuan,et al.Protection of Angelica sinensis polysaccharide on liver histological structure in mice injured by ephedrine[J].Acta Anatomica Sinica,2015,46(03):379-386.(in Chinese)
[12]ALKADI H O.Antimalarial drug toxicity:a review[J].Chemotherapy,2007,53:385-391.
[13]HIEN T T,WHITE N J.Qinghaosu[J].The Lancet,1993,341(8845):603-608.
[14]THOMAS G B,JAMES O P,STEPHEN J G,et al.Neurotoxicity in animals due to arteether and artemether[J].Transactions of the Royal Society of Tropical Medicine and Hygiene,1994,88(Supplement 1):33-36.
[15]赵艳红,王京燕.青蒿素类药物神经毒性及其作用机制[J].中国寄生虫学与寄生虫病杂志,2002,20(01):49-51.ZHAO Yan-hong,WANG Jing-yan.Neurotoxicity of artemisinin and its mechanism[J].Chinese Journalof Parasitology and Parasitic Diseases,2002,20(01):49-51.(in Chinese)
[16]PETRAS J M,KYLE D E,GETTAGACAMIN M,et al.Arteether:risks of two-week administration in Macaca mulatta[J].The American Journal of Tropical Medicine and Hygiene,1997,56(04):390-396.
[17]WESCHE D L,DECOSTER M A,TORTELLA F C,et al.Neurotoxicity of artemisinin analogs in vitro[J].Antimicrobial Agents and Chemotherapy,1994,38(08):1813-1819.
[18]BREWER T G,GRATE S J,PEGGINS J O,et al.Fatal neurotoxicity of arteether and artemether[J].The American Journal of Tropical Medicine and Hygiene,1994,51(03):251-259.
[19]U J H,ZHANG H D,MA Z J,et al.Artesunate induces on cosis-like cell death in vitro and has anti-tumor activity against pancreatic cancer xenografts in vivo[J].Cancer Chemotherapy and Pharmacology,2010,65(05):895-902.
[20]FINAURINI S,RONZONI L,COLANCECCO A,et al.Selective toxicity of dihydroartemisinin on human CD-34+erythroid cell differentiation[J].Toxicology,2010,276(02):128-134.
[2]KRISHNA S,BUSTAMANTE L,HAYNES R K,et al.Artemisinins:their growing importance in medicine[J].Trends in Pharmacological Sciences,2008,29(10):520-527.
[3]EFFERTH T,KAINA B.Toxicity of the antimalarial artemisinin and its dervatives[J].Critical Reviews in Toxicology,2010,40(05):405-421.
[4]潘存霞,刘卢生,张敏,等.青蒿提取物对獭兔的生长性能和免疫功能的影响[J].饲料博览(技术版),2007(06):9-12.PAN Cun-xia,LIU Lu-sheng,ZHANG Min,et al.Effects of sweet wormwood herb extracts on performance and immune function in rex rabbit[J].Feed Review(Technical Edition),2007(06):9-12.(in Chinese)
[5]韩洪英,陈东颖,全瑞兰,等.青蒿提取物作为饲料添加剂对断奶仔猪生产性能的影响[J].饲料工业,2011,32(06):5-6.HAN Hong-ying,CHEN Dong-ying,QUAN Rui-lan,et al.Effects of Artemisia annua extract as feed additive on performance of weaned piglets[J].Feed Industry,2011,32(06):5-6.(in Chinese)
[6]戴小军,刘延庆,梅全喜.蒿属药用植物药理活性研究进展[J].中药材,2005,28(03):243-247.DAI Xiao-jun,LIU Yan-qing,MEI Quan-xi.Advances in pharmacological activities of medicinal plants of Artemisia[J].Journal of Chinese Medicinal Materials,2005,28(03):243-247.(in Chinese)
[7]席世玲,高玲,赵瑾,等.青蒿素的药理作用及其在畜牧生产中的应用[J].上海畜牧兽医通讯,2009,(06):64-65.XI Shi-ling,GAO Ling,ZHAO Jin,et al.Pharmacological action of artemisinin and its application in animal production[J].Shanghai Journal of Animal Husbandry and Veterinary Medicine,2009,(06):64-65.(in Chinese)
[8]拜彬强,郝力壮,刘书杰,等.青蒿提取物对藏羊瘤胃体外产气发酵特性及甲烷产量的影响[J].江苏农业科学,2015,43(12):227-231.BAI Bin-qiang,HAO Li-zhuang,LIU Shu-jie,et al.Effects of artemisia annua extract on rumen gas production,fermentation characteristics and methane production in Tibetan Sheep[J].Jiangsu Agricultural Sciences,2015,43(12):227-231.(in Chinese)
[9]孙红梅,郝力壮,冯宇哲,等.青蒿提取物对牦牛瘤胃发酵及甲烷产量的影响[J].家畜生态学报,2015,36(08):34-40.SUN Hong-mei,HAO Li-zhuang,FENG Yu-zhe,et al.Effect of artemisinin on rumen fermentation and methane emissions of yak[J].Journal of Domestic Animal Ecology,2015,36(08):34-40.(in Chinese)
[10]《化学药物急性毒性试验技术指导原则》课题研究组.化学药物急性毒性试验技术指导原则[M].北京:中国医药科技出版社,2010:1-15.《Technical guidelines for acute toxicity test of chemical drugs》group of subject study.Technical Guidelines for Acute Toxicity Test of Chemical Drugs[M].Beijing:China Medical Science Press,2010:1-15.(in Chinese)
[11]孟茹,李重阳,俞诗源,等.当归(粗)多糖对麻黄素肝组织损伤的保护作用[J].解剖学报,2015,46(03):379-386.MENG Ru,LI Chong-yang,YU Shi-yuan,et al.Protection of Angelica sinensis polysaccharide on liver histological structure in mice injured by ephedrine[J].Acta Anatomica Sinica,2015,46(03):379-386.(in Chinese)
[12]ALKADI H O.Antimalarial drug toxicity:a review[J].Chemotherapy,2007,53:385-391.
[13]HIEN T T,WHITE N J.Qinghaosu[J].The Lancet,1993,341(8845):603-608.
[14]THOMAS G B,JAMES O P,STEPHEN J G,et al.Neurotoxicity in animals due to arteether and artemether[J].Transactions of the Royal Society of Tropical Medicine and Hygiene,1994,88(Supplement 1):33-36.
[15]赵艳红,王京燕.青蒿素类药物神经毒性及其作用机制[J].中国寄生虫学与寄生虫病杂志,2002,20(01):49-51.ZHAO Yan-hong,WANG Jing-yan.Neurotoxicity of artemisinin and its mechanism[J].Chinese Journalof Parasitology and Parasitic Diseases,2002,20(01):49-51.(in Chinese)
[16]PETRAS J M,KYLE D E,GETTAGACAMIN M,et al.Arteether:risks of two-week administration in Macaca mulatta[J].The American Journal of Tropical Medicine and Hygiene,1997,56(04):390-396.
[17]WESCHE D L,DECOSTER M A,TORTELLA F C,et al.Neurotoxicity of artemisinin analogs in vitro[J].Antimicrobial Agents and Chemotherapy,1994,38(08):1813-1819.
[18]BREWER T G,GRATE S J,PEGGINS J O,et al.Fatal neurotoxicity of arteether and artemether[J].The American Journal of Tropical Medicine and Hygiene,1994,51(03):251-259.
[19]U J H,ZHANG H D,MA Z J,et al.Artesunate induces on cosis-like cell death in vitro and has anti-tumor activity against pancreatic cancer xenografts in vivo[J].Cancer Chemotherapy and Pharmacology,2010,65(05):895-902.
[20]FINAURINI S,RONZONI L,COLANCECCO A,et al.Selective toxicity of dihydroartemisinin on human CD-34+erythroid cell differentiation[J].Toxicology,2010,276(02):128-134.