Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China.
J Ethnopharmacol. 2013 Aug 26;149(1):303-10. doi: 10.1016/j.jep.2013.06.039. Epub 2013 Jul 2.
BX is a traditional Chinese medicine (TCM) from the plant Pinellia ternata(Thunb.) Berit. It has been traditionally used to treat cough, vomiting, infection and inflammation. Despite of its potentially clinical utility, it also has many side effects and toxicity.
We propose here an ultra performance liquid chromatography coupled with quadrupole time-of-fight mass spectrometry (UPLC Q-TOF/MS) metabonomics approach to elucidate the toxicity in rats induced by orally administered BX in multiple organs including the kidney, liver, and heart.
Serum samples were collected from Sprague-Dawley male rats exposed to BX (6g/kg/day, n=10) and healthy controls (n=10) at the 48 h, 144 h, 240 h, and 336 h postdose for LC/MS analyses. Through principal component analysis and orthogonal partial least squares-discriminant analysis of the integrated serum MS data, we distinguished the BX group from the healthy control group and identified the differential metabolites and pertinent altered biological pathways in response to the herbal toxin. The liver, kidney, heart were assessed using conventional histopathological examinations at the end point of the experiment. The serum samples at the 336 h postdose were assessed using biochemistry test.
Significant differences in the serum levels of phospholipids, amino acids, L-carnitine and L-acetylcarnitine were observed in BX-induced rats, indicating the perturbations of phospholipid metabolism, amino acid metabolism and carnitine metabolism in BX-induced rats.
In the paper, we used metabonomics approach to study the toxicity of BX for the first time. With blood biochemistry, histopathological examinations and metabonomics methods, we validated that oral administration of crude BX caused no obvious liver and kidney toxicity in SD rats. BX may possess certain cardio toxicity in SD rats. The metabolism changes suggested that metabonomic approach was a promising tool to study and diagnose TCM-induced toxicity.
BX 是一种来自半夏（Pinellia ternata（Thunb.）Berit）的中药。它传统上用于治疗咳嗽、呕吐、感染和炎症。尽管它具有潜在的临床用途，但它也有许多副作用和毒性。
我们在这里提出了一种超高效液相色谱-四极杆飞行时间质谱联用（UPLC-Q-TOF/MS）代谢组学方法，以阐明口服 BX 对肾脏、肝脏和心脏等多个器官诱导的大鼠毒性。
将血清样品从暴露于 BX（6g/kg/天，n=10）和健康对照（n=10）的 Sprague-Dawley 雄性大鼠中收集，在给药后 48 h、144 h、240 h 和 336 h 进行 LC/MS 分析。通过对整合血清 MS 数据进行主成分分析和正交偏最小二乘判别分析，我们将 BX 组与健康对照组区分开来，并确定了对草药毒素的差异代谢物和相关改变的生物学途径。在实验结束时，使用常规组织病理学检查评估肝、肾、心。在给药后 336 h 评估血清样本，并进行生化测试。
在 BX 诱导的大鼠中，观察到磷脂、氨基酸、L-肉碱和 L-乙酰肉碱血清水平的显著差异，表明 BX 诱导的大鼠中磷脂代谢、氨基酸代谢和肉碱代谢受到干扰。
本文首次采用代谢组学方法研究 BX 的毒性。通过血液生化、组织病理学检查和代谢组学方法，我们验证了口服粗 BX 对 SD 大鼠无明显的肝、肾毒性。BX 可能对 SD 大鼠具有一定的心脏毒性。代谢变化表明，代谢组学方法是研究和诊断中药诱导毒性的一种有前途的工具。
