Sun Bo, Wu Shengming, Li Ling, Li Haijing, Zhang Qi, Chen Hebing, Li Famei, Dong Fangting, Yan Xianzhong
Department of Analytical Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, China.
Rapid Commun Mass Spectrom. 2009 Apr;23(8):1221-8. doi: 10.1002/rcm.3992.
A metabolomic investigation of intoxication with Aconitum sp. alkaloids was carried out. Plasma obtained from Wistar rats administered these alkaloids was analyzed using gas chromatography/time-of-flight mass spectrometry. Samples were analyzed following protein precipitation, liquid-liquid extraction, and derivatization. Thirty-six metabolites were identified among the detected compounds. Subsequent data analysis using the t test and principal component analysis revealed metabolic differences between the control rats and treated groups as well as between the groups of rats administered different alkaloids. Twenty-seven metabolites were significantly different between plasma samples from the controls and treated groups. The significant decreased plasma levels of glutamine and creatinine in all treated groups suggested impaired heart and muscle function caused by alkaloids. The plasma levels of 22 metabolites in the hypaconitine group were significantly decreased. In contrast, only 8 and 13 metabolites were observed with significantly decreased levels in the aconitine and mesaconitine groups, respectively.These results indicated that Aconitum sp. alkaloids can cause metabolic disorders in rats. The toxicity and corresponding mechanism of hypaconitine was different from those of aconitine and mesaconitine, based on the differences of perturbed metabolic patterns between groups.
开展了一项关于乌头属生物碱中毒的代谢组学研究。使用气相色谱/飞行时间质谱法对给予这些生物碱的Wistar大鼠的血浆进行分析。样品经蛋白质沉淀、液液萃取和衍生化后进行分析。在检测到的化合物中鉴定出36种代谢物。随后使用t检验和主成分分析进行数据分析，结果显示对照组大鼠与处理组之间以及给予不同生物碱的大鼠组之间存在代谢差异。对照组和处理组的血浆样品中有27种代谢物存在显著差异。所有处理组中谷氨酰胺和肌酐的血浆水平显著降低，提示生物碱导致心脏和肌肉功能受损。在次乌头碱组中，22种代谢物的血浆水平显著降低。相比之下，在乌头碱组和中乌头碱组中，分别仅观察到8种和13种代谢物水平显著降低。这些结果表明，乌头属生物碱可导致大鼠代谢紊乱。基于各组间代谢模式扰动的差异，次乌头碱的毒性及相应机制与乌头碱和中乌头碱不同。
