甲苯咪唑在异育银鲫体内代谢及肝毒性研究  

Metabolism and Hepatotoxicity of Mebendazole in Allogenic Silver Crucian Carp

作　　者：苏美珍 张祎桐 王浩[3] 吕利群[1] SU Meizhen;ZHANG Yitong;WANG Hao;LYU Liqun(National Pathogen Collection Center for Aquatic Animals, Shanghai Ocean University, Shanghai 201306, China;Key Laboratory of Freshwater Aquatic Genetic Resources for Aquaculture, Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China;National Experimental Teaching Demonstration Center for Fishery Sciences, Shanghai Ocean University, Shanghai 201306, China)

机构地区：[1]上海海洋大学,国家水生动物病原库,上海201306 [2]上海海洋大学,农业农村部淡水水产种质资源重点实验室,上海201306 [3]上海海洋大学,水产科学国家级实验教学示范中心,上海201306

出　　处：《水产科学》2020年第5期710-718,共9页Fisheries Science

基　　金：国家现代农业产业技术体系建设专项(CARS-45-19);第四届中国科协与中国水产学会青年人才托举工程项目(D-8005-19-0012)。

摘　　要：甲苯咪唑是淡水鱼类养殖上常用的一类广谱抗寄生虫药物,其在异育银鲫中的药物毒性仍不清楚。在水温(20±2)℃下,给体质量(90±20)g的异育银鲫用管灌入胃中甲苯咪唑,剂量为20、10、5 mg/kg,对照组口灌甲酸。给药后1、2、4、6、10、24、48、84 h,自鱼尾静脉取血,立即加入2%的草酸钾抗凝剂(抗凝剂∶血浆=1∶10,体积比)混匀,然后以4000 r/min离心10 min;给药后的0、24、48 h取肝胰脏和肾脏,测定超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化氢酶、谷草转氨酶、谷丙转氨酶和碱性磷酸酶的活性及超氧化物歧化酶、过氧化氢酶基因的表达量。试验结果表明,24 h时异育银鲫3个组织中甲苯咪唑含量达最大值,24 h后异育银鲫体内的甲苯咪唑则被逐渐代谢,肝胰脏中药物富集水平最高,其次是肾脏,血液最低。20 mg/kg的给药剂量甲苯咪唑在肝胰脏中的最高药物质量浓度约为肾脏的1.3倍,超过血液药物质量浓度约45倍。口灌20 mg/kg的甲苯咪唑鱼体肝胰脏中谷胱甘肽过氧化氢酶含量呈时间依赖性下降,碱性磷酸酶、过氧化氢酶、超氧化物歧化酶含量和血液中谷草转氨酶、谷丙转氨酶呈先升后降的趋势。口灌20 mg/kg的甲苯咪唑对各项检测指标均有负面影响,损伤了异育银鲫肝胰脏的正常解毒及抗氧化功能。本研究结果为甲苯咪唑药物在水产养殖中的安全使用提供了理论支撑。Allogenic silver crucian carp Carassius auratus gibelio with body weight of(90±20)g was intragastrically administered with mebendazole at a dose of 20 mg/kg,10 mg/kg or 5 mg/kg,while the control group was orally administered with formic acid,at water temperature of(20±2)℃and blood was collected from caudal vein at 1,2,4,6,10,24,48 and 84 hours after administration.Potassium oxalate anticoagulant(anticoagulant∶plasma=1∶10,V/V)was added immediately into the blood samples which then were centrifugated at 4000 rpm for 10 min.The activities of superoxide dismutase(SOD),catalase(CAT),glutathione catalase(GSH-PX),glutathione transaminase(AST),alanine aminotransferase(ALT)and alkaline phosphatase(AKP)and the transcriptional expression levels of SOD and CAT genes were compared in the hepatopancreas and kidney of allogenic silver crucian carp at 0,24 and 48 hours after administration.It was found that there were similar changes in the three tissues after administration,with the maximal content of mebendazole in three tissues of crucian carp in 24 hours,and then gradually metabolized,with the maximum in hepatopancreas,followed by kidney,and the minimum in blood.The maximal concentration of mebendazole in hepatopancreas was about 1.3 times as that in kidney and 45 times as that in blood under administration at 20 mg/kg.The contents of glutathione catalase in liver and pancreas of tobendazole-treated fish were decreased in a time-dependent manner,while the activities of alkaline phosphatase,catalase,superoxide dismutase,glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase in blood were increased first and then decreased.The findings indicated that oral administration of 20 mg/kg mebendazole had a negative impact on various indicators,damaging normal detoxification and antioxidant function,which provides theoretical support for the safe use of mebendazole in aquaculture.

关 键 词：甲苯咪唑 异育银鲫 酶活性 肝毒性 药代动力学 

分 类 号：S948[农业科学—水产养殖]