Gas chromatography time-of-flight mass spectrometry based metabolomic approach to evaluate acute toxicity of triptolide in rats

To evaluate toxicity in rats after orally giving triptolide by using the gas chromatography time-of-flight mass spectrometry(GC/TOF-MS)based metabolomics approach. Potential biomarkers identified here paved a way to new implications of clinical early prevention and diagnosis of safety. In this study, SD rats were randomly divided into four groups, that included high dose(2. 4 mg/kg), medium dose(1. 2 mg/kg), low dose(0. 6 mg/kg)and control groups, respectively. Following by single orally dosing, urine, serum and tissue sample were collected, respectively on day 0, day 1, day 3 and day 7 for a subsequent metabolomic bioanalysis. Multivariate data analysis was then used to process the data which indicated excellent separation between different doses and treatment days. The metabolic pattern after treatment with triptolide at high and medium dose visually depicted the occurrence, development and recovery process of toxicity that vividly demonstrated dose and time-dependent toxicity following different dose of triptolide in rats. Metabolomic results were consistent with those obtained from the routine biochemical assays and histopathological characterization. The results indicated that malate, citrate, taurine, glutamate, threonine and stearic acid, etc. could serve as potential toxicity biomarkers. Our study indicated that a metabolomic method established in this study provided a promising and effective approach to evaluate the mechanism of toxicity and the mechanism of hepatotoxicity was related with the impairment mitochondria, tricarboxylic acid cycle, amino acids and free fatty acids metabolism.