Hu Cong, Li Hong-Wei, Ke Jia-Qun, Yu Xue-Chun, Zhao Mei-Yu, Shi Xin-Yue, Wu Lin-Jing, Tang Xi-Lan, Xiong Yin-Hua
School of Pharmacy, 177505Jiangxi Science and Technology Normal University, Nanchang, P.R. China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221108320. doi: 10.1177/09603271221108320.
Chlorpromazine hydrochloride (CH) and -acetyl--amino-phenoltriptolide (APAP) are typical acentral dopamine receptor antagonists and antipyretic analgesics in clinical applications, respectively. However, it has been reported that these 2 drugs could cause liver damage. Lysophosphatidylcholines (LPCs) have multiple physiological functions and are metabolized primarily in the liver, where it undergoes significant changes when the liver is damaged. In the study, 15 LPCs in the rat serum with CH- and APAP-induced liver injury were quantified based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry, and multivariate statistical analyses including principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA) were combined to understand CH- and APAP-induced liver injury from the perspective of LPC metabolic profiling. The quantitative results showed that there were significant changes in 10 LPCs and 5 LPCs after CH- and APAP-administration, separately. The results of PCA and OPLS-DA indicated that CH- and APAP-induced liver injury could be well distinguished by the LPC metabolic profiling, and 7 LPCs and 1 LPC biomarkers that could characterize CH- and APAP-induced liver damage in turn had been screened. This study will not only provide a new perspective for the clinical diagnosis of CH- and APAP-induced liver injury, but also offer a reference for further study of their hepatotoxicity mechanisms.
盐酸氯丙嗪(CH)和对乙酰氨基酚(APAP)分别是临床应用中典型的中枢多巴胺受体拮抗剂和解热镇痛药。然而,已有报道称这两种药物会导致肝损伤。溶血磷脂酰胆碱(LPCs)具有多种生理功能,主要在肝脏中代谢,当肝脏受损时其会发生显著变化。在本研究中,基于超高效液相色谱四极杆飞行时间质谱对CH和APAP诱导肝损伤大鼠血清中的15种LPCs进行定量,并结合主成分分析(PCA)和正交偏最小二乘法判别分析(OPLS-DA)等多元统计分析方法,从LPC代谢谱的角度了解CH和APAP诱导的肝损伤。定量结果显示,给予CH和APAP后,分别有10种和5种LPCs发生了显著变化。PCA和OPLS-DA结果表明,CH和APAP诱导的肝损伤可以通过LPC代谢谱很好地区分,并且依次筛选出了7种和1种可表征CH和APAP诱导肝损伤的LPC生物标志物。本研究不仅为CH和APAP诱导肝损伤的临床诊断提供了新的视角,也为进一步研究其肝毒性机制提供了参考。