Research Paper Volume 13, Issue 14 pp 18669—18688

Plasma metabolites changes in male heroin addicts during acute and protracted withdrawal

Yong Zhou1,2, *, , Zhenrong Xie1,2, *, , Zunyue Zhang1,2, , Jiqing Yang1,2, , Minghui Chen1,3, , Fengrong Chen1,2, , Yuru Ma1,2, , Cheng Chen1,2,4, , Qingyan Peng1,2, , Lei Zou1,2, , Jianyuan Gao1,2, , Yu Xu1,4, , Yiqun Kuang1,2, , Mei Zhu1, , Dingyun You5, , Juehua Yu1,2, , Kunhua Wang1,6, &, ,

  • 1 NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
  • 2 Centre for Experimental Studies and Research, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
  • 3 Medical School, Kunming University of Science and Technology, Kunming 650032, Yunnan, China
  • 4 Yunnan Institute of Digestive Disease, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
  • 5 School of Public Health, Kunming Medical University, Kunming 650032, Yunnan, China
  • 6 Yunnan University, Kunming 650032, Yunnan, China
* Equal contribution

Received: March 26, 2021       Accepted: June 25, 2021       Published: July 19, 2021      

https://doi.org/10.18632/aging.203311
How to Cite

Copyright: © 2021 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Heroin addiction and withdrawal have been associated with an increased risk for infectious diseases and psychological complications. However, the changes of metabolites in heroin addicts during withdrawal remain largely unknown.

Methods: A total of 50 participants including 20 heroin addicts with acute abstinence stage, 15 with protracted abstinence stage and 15 healthy controls, were recruited. We performed metabolic profiling of plasma samples based on ultraperformance liquid chromatography coupled to tandem mass spectrometry to explore the potential biomarkers and mechanisms of heroin withdrawal.

Results: Among the metabolites analyzed, omega-6 polyunsaturated fatty acids (linoleic acid, dihomo-gamma-linolenic acid, arachidonic acid, n-6 docosapentaenoic acid), omega-3 polyunsaturated fatty acids (docosahexaenoic acid, docosapentaenoic acid), aromatic amino acids (phenylalanine, tyrosine, tryptophan), and intermediates of the tricarboxylic acid cycle (oxoglutaric acid, isocitric acid) were significantly reduced during acute heroin withdrawal. Although majority of the metabolite changes could recover after months of withdrawal, the levels of alpha-aminobutyric acid, alloisoleucine, ketoleucine, and oxalic acid do not recover.

Conclusions: In conclusion, the plasma metabolites undergo tremendous changes during heroin withdrawal. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and withdrawal stages in heroin addicts.

Abbreviations

Fas: fatty acids; PUFAs: polyunsaturated fatty acids; AD: Alzheimer’s disease; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; DPA: docosapentaenoic acid; AAs: Amino acids; OAs: organic acids; UPLC-MS/MS: ultraperformance liquid chromatography coupled to tandem mass spectrometry; SCFAs: short-chain fatty acids; LA: linoleic acid; TCA: tricarboxylic acid.