陈芳梅;陈隽;谢平;李伟;于源华;张晓;韩雪荣;于欣冉;

• 1:长春理工大学生命科学技术学院
• 2:中国科学院水生生物研究所

摘要(Abstract)：

基于谷胱甘肽(GSH)解毒作用探讨了微囊藻毒素-RR(MCRR)在不同动物肝脏和肾脏合作下的代谢机制。通过人工合成MCRR的谷胱甘肽代谢物(MCRR-GSH),腹腔注射至鲫鱼和大鼠体内,利用液相色谱串联质谱技术(LC-MS/MS)定量检测MCRR-GSH及其下游半胱氨酸代谢物(MCRR-Cys)在组织内的代谢动力学变化。在72 h的暴露实验中,实验组鲫鱼和大鼠体内均定量检测到MCRR-GSH和MCRR-Cys。MCRR-GSH在肾脏中的浓度显著高于其他组织(P<0.05),鲫鱼和大鼠体内累积浓度分别是(0.161±0.001)和(0.116±0.005)μg·g~(-1)DW。同样的,MCRR-Cys主要分布于鲫鱼和大鼠的肾脏组织。鲫鱼肾脏中MCRR-Cys的浓度出现明显的波动,而肝脏和胆汁内的MCRR-Cys浓度却呈现出上升的趋势;大鼠肾脏内MCRR-Cys的浓度呈缓慢下降的趋势,浓度范围为(8.899±0.817)μg·g~(-1)DW至(3.336±0.263)μg·g~(-1)DW。基于以上结果推测,微囊藻毒素在肝脏和肾脏合作下的解毒过程为:MC在肝脏内经GSH结合作用生成的代谢物MC-GSH随血液循环转运至肾脏,在肾脏内MCGSH快速地转化为下游代谢物MC-Cys以促进排泄。

关键词(KeyWords)： 微囊藻毒素;鲫鱼;大鼠;谷胱甘肽;解毒机制;高效液相色谱-质谱联用

Abstract:

Keywords:

基金项目(Foundation): 长春理工大学青年基金项目(XQNJJ-2016-16);; 吉林省大学生创新创业训练计划项目(2017S065)

作者(Author): 陈芳梅;陈隽;谢平;李伟;于源华;张晓;韩雪荣;于欣冉;

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DOI:

参考文献(References)：

• [1]周伦,鱼达,余海,等.饮用水源中的微囊藻毒素与大肠癌发病的关系[J].中华预防医学杂志,2000,34(4):224-226Zhou L,Yu D,Yu H,et al.Drinking water types,microcystins and colorectal cancer[J].Chinese Journal of Preventive Medicine,2000,34(4):224-226(in Chinese)
• [2]乐亚玲,刘利平.微囊藻毒素毒理学的研究进展[J].环境与健康杂志,2011,28:553-556Yue Y L,Liu L P.Progress on toxicological studies on microcystins[J].Journal of Environment and Health,2011,28:553-556(in Chinese)
• [3]谢平.水生动物体内的微囊藻毒素及其对人类健康的潜在威胁[M].北京:科学出版社,2006:52Xie P.Microcystins in Aquatic Animals with Potential Risk to Human Health[M].Beijing:Science Press,2006:52(in Chinese)
• [4]Chen J,Xie P,Li L,et al.First identification of the hepatotoxic microcystins in the serum of a chronically exposed human population together with indication of hepatocellular damage[J].Toxicology Sciences,2009,108:81-89
• [5]Zhang D,Xie P,Chen J,et al.Determination of microcystin-LR and its metabolites in snail(Bellamya aeruginosa),shrimp(Macrobrachium nipponensis)and silver carp(Hypophthalmichthys molitrix)from Lake Taihu,China[J].Chemosphere,2009,76:974-981
• [6]Hermansky S J,Stohs S J,Eldeen Z M,et al.Evaluation of potential chemoprotectants against microcystin-LR hepatotoxicity in mice[J].Journal of Applied Toxicology,1991,11(1):65-73
• [7]Pflugmacher S,Wiegand C,Beattie A.Uptake,effects,and metabolism of cyanobacterial toxins in the emergent reed plant Phragmites australis(Cav.)Trin.ex Steud[J].Environmental Toxicology and Chemistry,2001,20:846-852
• [8]Takenaka S.Covalent glutathione conjugation to cyanobacterial hepatotoxin microcystin LR by F344 rat cytosolic and microsomal glutathione S-transferases[J].Environmental Toxicology and Pharmacology,2001,9:135-139
• [9]Ito E,Takai A,Kondo F,et al.Comparison of protein phosphatase inhibitory activity and apparent toxicity of microcystins and related compounds[J].Toxicon Official Journal of the International Society on Toxinology,2002,40:1017-1025
• [10]Wu L,Xie P,Chen J,et al.Development and validation of a liquid chromatography-tandem mass spectrometry assay for the simultaneous quantitation of microcystin-RR and its metabolites in fish liver[J].Journal of Chromatography A,2010,1217:1455-1460
• [11]Zhang D,Yang Q,Xie P,et al.The role of cysteine conjugation in the detoxification of microcystin-LR in liver of bighead carp(Aristichthys nobilis):A field and laboratory study[J].Ecotoxicology,2012,21:244-252
• [12]He J,Chen J,Xie P,et al.Quantitatively evaluating detoxification of the hepatotoxic microcystins through the glutathione and cysteine pathway in the cyanobacteriaeating bighead carp[J].Aquatic Toxicology,2012,116:61-68
• [13]Li W,Xie P,Chen J,et al.Quantitative liquid chromatography-tandem mass spectrometry method for determination of microcystin-RR and its glutathione and cysteine conjugates in fish plasma and bile[J].Journal of Chromatography B-Analytical Technologies in the Biomedicaland Life Sciences,2014,963:113-118
• [14]Li W,Chen J,Xie P,et al.Rapid conversion and reversible conjugation of glutathione detoxification of microcystins in bighead carp(Aristichthys nobilis)[J].Aquatic Toxicology,2014,147:18-25
• [15]Fischer W J,Altheimer S,Cattori V,et al.Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin[J].Toxicology and Applied Pharmacology,2005,203:257-263
• [16]Hagenbuch B,Meier P.The superfamily of organic anion transporting polypeptides[J].Biochimica et Biophysica Acta(BBA)-Biomembranes,2003,1609:1-18
• [17]Kera Y,Liu Z,Matsumoto T,et al.Rat and human membrane dipeptidase:Tissue distribution and developmental changes[J].Comparative Biochemistry and Physiology B:Biochemistry and Molecular Biology,1999,123:53-58
• [18]van Bladeren B.Glutathione conjugation as a bioactivation reaction[J].Chemical-Biological Interactions,2000,129:61-76
• [19]Elfarra A A,Anders M W.Renal processing of glutathione conjugates.Role in nephrotoxicity[J].Biochemical Pharmacology,1984,33:3729-3732
• [20]Tal A,Romano M L,Stephenson G R,et al.Glutathione conjugation:A detoxification pathway for fenoxaprop-ethyl in barley,crabgrass,oat and wheat[J].Biochemical Pharmacology,1993,46:190-199
• [21]SzotákováB,BártíkováH,HlaváˇcováJ,et al.Inhibitory effect of anthocyanidins on hepatic glutathione Stransferase,UDP-glucuronosyltransferase and carbonyl reductase activities in rat and human[J].Xenobiotica,2013,43:679-685
• [22]Chen M,Lou Y,Wu Y D,et al.Characterization of in vivo and in vitro metabolites of furanodiene in rats by high performance liquid chromatography-electrospray ionization mass spectrometry and nuclear magnetic resonance spectra[J].Journal of Pharmaceutical and Biomedical Analysis,2013,86:161-168