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Metabolomics Analysis: Opioid Addiction Project (Golestan Cohort Study) - NMR (part-II)

ABSTRACT: Drug addiction is a major threat to the public health in the US and many other countries. Opioid abuse is associated with increased risks for cancer, psychological complications, heart and lung disease, and infections of the liver and blood. Because metabolites are intrinsically involved in multiple metabolic pathways in vivo, the relative quantification of metabolites in body fluids (for example urine) can provide a profile of the metabolic state of an organism. Metabolomics is a powerful technique for revealing the impact of exposure on the overall biochemistry of an individual or system. Opioids can modify the output of urinary metabolites through many integrated neural and hormonal mechanisms within the periphery, central nervous system, and kidneys. Opioids modulate the expression of genes involved in neuroplasticity through epigenetic and possibly RNA modifications, ultimately change the intracellular signaling cascades and dysfunction, and cause long-lasting changes in metabolome. The objective of this study is to identify how opium impacts metabolic pathways to provide markers of abuse, long-term opium addiction, the addiction molecular pathway, and unknown metabolites that are important to differentiation of the study phenotypes. To reach these goals in the present study, the urine specimens of opium abusers and non-users as controls was profiled using an untargeted nuclear magnetic resonance spectroscopy (NMR) metabolomics platform at University of North Carolina at Chapel Hill. The Golestan Cohort Study is conducted in Northeast of Iran to primarily study the risk factors for upper gastrointestinal cancers in this high-risk region, in which about 50,000 volunteers were analyzed for opium users and their mortality. More than 8,000 of participants (17%) age 40-75 reported opium use with a mean duration of 12.7 years. Opium was either smoked or orally consumed. The participants were selected from the cohort stratified by opium use patterns and tobacco use.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Urine

DISEASE(S): Addiction

SUBMITTER: Susan Sumner

PROVIDER: ST001619 | MetabolomicsWorkbench | Tue Dec 01 00:00:00 GMT 2020

REPOSITORIES: MetabolomicsWorkbench

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Project description:Drug addiction is a major threat to the public health in the US and many other countries. Opioid abuse is associated with increased risks for cancer, psychological complications, heart and lung disease, and infections of the liver and blood. Because metabolites are intrinsically involved in multiple metabolic pathways in vivo, the relative quantification of metabolites in body fluids (for example urine) can provide a profile of the metabolic state of an organism. Metabolomics is a powerful technique for revealing the impact of exposure on the overall biochemistry of an individual or system. Opioids can modify the output of urinary metabolites through many integrated neural and hormonal mechanisms within the periphery, central nervous system, and kidneys. Opioids modulate the expression of genes involved in neuroplasticity through epigenetic and possibly RNA modifications, ultimately change the intracellular signaling cascades and dysfunction, and cause long-lasting changes in metabolome. The objective of this study is to identify how opium impacts metabolic pathways to provide markers of abuse, long-term opium addiction, the addiction molecular pathway, and unknown metabolites that are important to differentiation of the study phenotypes. To reach these goals in the present study, the urine specimens of opium abusers and non-users as controls will be profiled using an untargeted liquid chromatography mass spectrometric (LC-MS/MS) at University of North Carolina at Chapel Hill. The Golestan Cohort Study is conducted in Northeast of Iran to primarily study the risk factors for upper gastrointestinal cancers in this high-risk region, in which about 50,000 volunteers were analyzed for opium users and their mortality. More than 8,000 of participants (17%) age 40-75 reported opium use with a mean duration of 12.7 years. Opium was either smoked or orally consumed. The participants were selected from the cohort stratified by opium use patterns and tobacco use.

Project description:The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. We assessed the impact of prenatal exposure to arsenic on genome-wide miRNA expression profiles and their potential influence on gene expression patterns in the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort. This cohort includes residents from Gómez Palacio, located in the state of Durango in the Lagunera region of Northern Mexico. A total of 200 pregnant women residing in Gómez Palacio, State of Durango, Mexico, were recruited at the General Hospital of Gómez Palacio to participate in the BEAR prospective pregnancy cohort. The present study focuses on miRNA expression profiles and utilizes 40 samples obtained from mother-newborn pairs selected from the larger cohort (n=200). The subcohort was selected to include subjects exposed to varying levels of arsenic as determined by both total arsenic in maternal urine (U-tAs) and inorganic arsenic in drinking water (DW-iAs). Cord blood samples were collected from the newborns immediately after infant delivery. Blood samples were collected using PreAnalytix PaxGene RNA tubes and extracted using the PAXgene RNA Kit, per standard protocol (Qiagen, Valencia, CA). Isolated RNA used for microarray analysis were amplified and labeled using the NuGEN Ovation Pico WTA System V2 and Encore Biotin Module, respectively (NuGEN, San Carlos, CA). RNA isolated from 40 cord blood samples were labeled and hybridized to the Agilent Human miRNA Microarray, based off miRBase v16.0.

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Metabolomics Analysis: Opioid Addiction Project (Golestan Cohort Study) - NMR (part-II)

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