Identification of Morphine and Heroin-Treatment in Mice Using Metabonomics
Wuhuan Lu,
Ran Zhang,
Wei Sheng,
Luohua Feng,
Peng Xu,
Youmei Wang,
Yuan Xie,
Hui Xu,
Guangji Wang,
Jiye Aa
Affiliations
Wuhuan Lu
Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
Ran Zhang
Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
Wei Sheng
Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
Luohua Feng
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
Peng Xu
China National Narcotics Control Commission—China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, No. 24 Tongjiaxiang Road, Nanjing 210009, China
Youmei Wang
China National Narcotics Control Commission—China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, No. 24 Tongjiaxiang Road, Nanjing 210009, China
Yuan Xie
Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
Hui Xu
Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
Guangji Wang
Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
Jiye Aa
Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
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−1 (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.
