Investigation of toxicological effects of Shuanghuanglian injection in Beagle dogs by metabonomic and traditional approaches
Investigation of toxicological effects of Shuanghuanglian injection in Beagle dogs by metabonomic and traditional approaches
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DOI：
10.1258/ebm.2010.009390
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发表时间：
2010-11
影响因子：
3.2
通讯作者：
Guangyan Yan;Yinglan Zhao;Pengchi Deng;L. Lv;Yanli Wang;Q. Bu;B. Liu;Chunyan Hu;Yanqiang Zhuo;Xunning Yang;Li Wang;X. Cen
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文献类型：
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作者：
Guangyan Yan;Yinglan Zhao;Pengchi Deng;L. Lv;Yanli Wang;Q. Bu;B. Liu;Chunyan Hu;Yanqiang Zhuo;Xunning Yang;Li Wang;X. Cen
本研究采用临床生化、血液学、组织病理学和基于1H核磁共振波谱的代谢组学方法，研究双黄连注射液静脉给药（剂量分别为4、12和36 mL /kg）后30 d对Beagle犬的毒理学效应。高剂量组红细胞、血红蛋白、平均细胞体积、平均红细胞血红蛋白和平均红细胞血红蛋白浓度均降低。网织红细胞、总胆红素和直接胆红素均升高。高剂量组动物肝脏、脾脏和肾脏均可见明显含铁血黄素沉着和普鲁士蓝阳性，透射电镜检查显示肝脏内有相当数量的无红细胞。这些结果共同表明SHL注射有可能引起溶血性贫血。代谢组学分析显示，治疗组血清乳酸、胆碱和磷胆碱升高，而牛磺酸降低，这些发现可能是SHL注射液毒理学机制的基础。综上所述，SHL注射对Beagle犬有溶血作用；此外，血清胆碱、磷胆碱以及乳酸和牛磺酸可能是SHL注射液所致溶血性贫血的生物标志物。
In this study, clinical biochemistry, hematology, histopathology and 1H nuclear magnetic resonance spectroscopy-based metabonomic approaches were applied to investigate the toxicological effects of Shuanghuanglian (SHL) injection after intravenous administration (dosed at 4, 12 and 36 mL stock/kg) in Beagle dogs for 30 d. Decreases in red blood cells, hemoglobin, mean cell volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were observed in the high-dose group. Elevated reticulocytes, total bilirubin and direct bilirubin were also observed in this group. Moreover, significant hemosiderosis and Prussian blue positivity were detected in the liver, spleen and kidney from high-dose group animals, and transmission electron microscopy examination revealed an appreciable number of acanthrocytes in the liver. These results collectively indicate that SHL injection has the potential to cause hemolytic anemia. Metabonomic analysis showed increases in serum lactate, choline and phosphocholine but a decrease in taurine in treated groups and these findings may underlie the toxicological mechanism of SHL injection. In summary, SHL injection shows hemolytic effects in Beagle dogs; moreover, serum choline and phosphocholine as well as lactate and taurine may be the biomarkers for hemolytic anemia induced by SHL injection.