Lu Wuhuan, Zhang Ran, Sheng Wei, Feng Luohua, Xu Peng, Wang Youmei, Xie Yuan, Xu Hui, Wang Guangji, Aa Jiye
Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Metabolites. 2021 Sep 7;11(9):607. doi: 10.3390/metabo11090607.
Although heroin and morphine are structural analogues and morphine is a metabolite of heroin, it is not known how the effect of each substance on metabolites in vivo differs. Heroin and morphine were administered to C57BL/6J mice in increasing doses from 2 to 25 and 3 to 9 mg kg (twice a day, i.p.), respectively, for 20 days. The animals underwent withdrawal for 5 days and were readministered the drugs after 10 days. Serum and urine analytes were profiled using gas chromatography-mass spectrometry (GC-MS), and metabolic patterns were evaluated based on metabonomics data. Metabonomics data showed that heroin administration changed metabolic pattern, and heroin withdrawal did not quickly restore it to baseline levels. A relapse of heroin exposure changed metabolic pattern again. In contrast, although the administration of morphine changed metabolic pattern, whether from morphine withdrawal or relapse, metabolic pattern was similar to control levels. The analysis of metabolites showed that both heroin and morphine interfered with lipid metabolism, the tricarboxylic acid (TCA) cycle and amino acid metabolism. In addition, both heroin and morphine increased the levels of 3-hydroxybutyric acid and citric acid but decreased the serum levels of 2-ketoglutaric acid and tryptophan. Moreover, heroin and morphine reduced the levels of aconitic acid, cysteine, glycine, and oxalic acid in urine. The results show 3-Hydroxybutyric acid, tryptophan, citric acid and 2-ketoglutaric acid can be used as potential markers of opiate abuse in serum, while oxalic acid, aconitic acid, cysteine, and glycine can be used as potential markers in urine.
尽管海洛因和吗啡是结构类似物，且吗啡是海洛因的代谢产物，但尚不清楚每种物质对体内代谢物的影响有何不同。分别以2至25毫克/千克和3至9毫克/千克的递增剂量给C57BL/6J小鼠腹腔注射海洛因和吗啡（每天两次），持续20天。让动物戒断5天，10天后再次给药。使用气相色谱-质谱联用仪（GC-MS）对血清和尿液分析物进行分析，并根据代谢组学数据评估代谢模式。代谢组学数据表明，给予海洛因会改变代谢模式，而海洛因戒断后不会迅速恢复到基线水平。再次接触海洛因会使代谢模式再次改变。相比之下，尽管给予吗啡会改变代谢模式，但无论是吗啡戒断还是复发，代谢模式都与对照水平相似。代谢物分析表明，海洛因和吗啡均会干扰脂质代谢、三羧酸（TCA）循环和氨基酸代谢。此外，海洛因和吗啡都会增加3-羟基丁酸和柠檬酸的水平，但会降低血清中2-酮戊二酸和色氨酸的水平。此外，海洛因和吗啡会降低尿液中乌头酸、半胱氨酸、甘氨酸和草酸的水平。结果表明，3-羟基丁酸、色氨酸、柠檬酸和2-酮戊二酸可作为血清中阿片类药物滥用的潜在标志物，而草酸、乌头酸、半胱氨酸和甘氨酸可作为尿液中的潜在标志物。
