Metabolomics Analysis of Opiate Abusers from Golestan Cohort Study (GCS)
Authors: Ghanbari Reza , Pathmasiri Wimal , McRitchie Susan , Stewart Delisha , Etemadi Arash , Abnet Christian , Pollock Jonathan , Malekzadeh Reza , Sumner Susan 
Published: June 2021

Illicit use of opiate is a major public health threat across the world, and is associated with numerous potential adverse health outcomes such as cancers, infectious diseases and psychological disorders. Opium and their derivatives can modulate gene expression through epigenetic and possibly RNA modifications, ultimately impacts intracellular signaling cascades, and creates long‐lasting changes in the metabolome. Furthermore opiate can modify the output of urinary metabolites through many integrated neural and hormonal mechanisms within the periphery and central nervous system and kidneys.Metabolomics is a powerful technique that has been used in clinical and laboratory medicine for the discovery of potential diagnostic, prognostic and therapeutic biomarkers. The result of this study could lead to identification of significant altered biomarkers and can improve our knowledge of underling etiology and molecular pathways of opiate addiction and inform nutrition intervention.We performed 1H‐NMR metabolomics and liquid chromatography mass spectrometry (UPLC‐Q Exactive HF‐X MS) to analyze the urine metabolite profiling of 535 individuals from Golestan Cohort Study (GCS). The GCS is conducted in northeast of Iran to assess risk factors for upper gastrointestinal cancers for more than 50,000 volunteers who also were analyzed for opiate use and their complications.The metabolomics profiles of urine specimens from 443 (285 daily and 158 non‐daily) opiate users, stratified by route of use (oral and smoking) and tobacco use, have been compared with profiles obtained for 92 nonuser controls. After sample preparation, data was collected using a Bruker Avance III 700 MHz NMR Spectrometer. TopSpin and ACD Spectrus Processor softwares were used to data processing and NMR binning. Metabolites were identified by using Chenomx NMR Suite 8.3 Professional software.Metabolomics analysis revealed perturbations in level of hydroxyisovalerate, alanine, choline, citrate, creatinine, glucose, lactate, malonate, methylhydantoin, phenylalanine, phosphocholine, sucrose, tyrosine, acetylsalicylate and inositol in opiate abuser versus control groups.Metabolites are intrinsically involved in multiple metabolic pathways in vivo, so relative quantification of metabolites in body fluids such as urine can provide a profile of the metabolic state of an organism. Over the past decade, a large number of prospective and retrospective epidemiological studies have investigated the potential carcinogenic effect of opiate in humans. While data in favor of opiate's carcinogenicity is mounting, the potential mechanisms are largely unclear. The present study will explore opiate addiction and cancer risk using metabolomics, including exploring opiate effects on metabolic pathways and identification of potential markers of long term opiate abuse.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.