Phosphatidylethanol in whole blood of rhesus monkeys correlates with ethanol consumption
Background Phosphatidylethanol (PEth) homologs are ethanol metabolites used to identify and monitor alcohol drinking in humans. In this study, we measured levels of the 2 most abundant homologs, PEth 16:0/18:1 and PEth 16:0/18:2, in whole blood samples from rhesus macaque monkeys that drank ethanol...
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| Veröffentlicht in: | Alcoholism, clinical and experimental research clinical and experimental research, 2021-04, Vol.45 (4), p.689-696 |
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| creator | Lopez‐Cruzan, Marisa Walter, Nicole A. R. Sanchez, Jesus J. Ginsburg, Brett C. Koek, Wouter Jimenez, Vanessa A. Grant, Kathleen A. Javors, Martin A. |
| description | Background
Phosphatidylethanol (PEth) homologs are ethanol metabolites used to identify and monitor alcohol drinking in humans. In this study, we measured levels of the 2 most abundant homologs, PEth 16:0/18:1 and PEth 16:0/18:2, in whole blood samples from rhesus macaque monkeys that drank ethanol daily ad libitum to assess the relationship between PEth levels and recent ethanol exposure in this animal model.
Methods
Blood samples were obtained from The Monkey Alcohol Tissue Research Resource. The monkeys were first induced to consume 4% (w/v) ethanol in water from a panel attached to their home cage. Then, monkeys were allowed to drink ethanol and water ad libitum 22 h daily for 12 months and the daily amount of ethanol each monkey consumed was measured. Whole, uncoagulated blood was collected from each animal at the end of the entire experimental procedure. PEth 16:0/18:1 and PEth 16:0/18:2 levels were analyzed by HPLC with tandem mass spectrometry, and the ethanol consumed during the preceding 14 days was measured. Combined PEth was the sum of the concentrations of both homologs.
Results
Our results show that (1) PEth accumulates in the blood of rhesus monkeys after ethanol consumption; (2) PEth homolog levels were correlated with the daily average ethanol intake during the 14‐day period immediately preceding blood collection; (3) the application of established human PEth 16:0/18:1 cutoff concentrations indicative of light social or no ethanol consumption ( |
| doi_str_mv | 10.1111/acer.14584 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8150885</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2492289922</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4484-47209f6c3ecba700c3e27afb662631005237e7f1181784418f2840767d3d71e3</originalsourceid><addsrcrecordid>eNp9kU2LFDEQhoMo7rh68QdIwIsIvVY-OslchGVYP2BBkT14C5l0tZ013RmTbof592ad3UU9mEMlVJ48VHgJec7gjNX1xnnMZ0y2Rj4gK9YKaIBr_ZCsoDYbBWBOyJNSrgFAGqUekxMhFFOc6RX5-nlIZTe4OXSHiPPgphRpmOh-SBHpNqbU0dTTPGBZCh3T9B0PhfqUM0Y3Y6H7MA_07qFPU1nG3RzS9JQ86l0s-Ox2PyVX7y6uNh-ay0_vP27OLxsvpZGN1BzWvfIC_dZpgHrg2vVbpbgSDKDlQqPuGTNMGymZ6bmRoJXuRKcZilPy9qjdLdsRO4_TnF20uxxGlw82uWD_vpnCYL-ln9awFoxpq-DVrSCnHwuW2Y6heIzRTZiWYrlcc27WtVT05T_odVryVH9necs0F6KFdaVeHymfUykZ-_thGNibvOxNXvZ3XhV-8ef49-hdQBVgR2AfIh7-o7Lnm4svR-kvpoCg9A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2517233509</pqid></control><display><type>article</type><title>Phosphatidylethanol in whole blood of rhesus monkeys correlates with ethanol consumption</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Lopez‐Cruzan, Marisa ; Walter, Nicole A. R. ; Sanchez, Jesus J. ; Ginsburg, Brett C. ; Koek, Wouter ; Jimenez, Vanessa A. ; Grant, Kathleen A. ; Javors, Martin A.</creator><creatorcontrib>Lopez‐Cruzan, Marisa ; Walter, Nicole A. R. ; Sanchez, Jesus J. ; Ginsburg, Brett C. ; Koek, Wouter ; Jimenez, Vanessa A. ; Grant, Kathleen A. ; Javors, Martin A.</creatorcontrib><description>Background
Phosphatidylethanol (PEth) homologs are ethanol metabolites used to identify and monitor alcohol drinking in humans. In this study, we measured levels of the 2 most abundant homologs, PEth 16:0/18:1 and PEth 16:0/18:2, in whole blood samples from rhesus macaque monkeys that drank ethanol daily ad libitum to assess the relationship between PEth levels and recent ethanol exposure in this animal model.
Methods
Blood samples were obtained from The Monkey Alcohol Tissue Research Resource. The monkeys were first induced to consume 4% (w/v) ethanol in water from a panel attached to their home cage. Then, monkeys were allowed to drink ethanol and water ad libitum 22 h daily for 12 months and the daily amount of ethanol each monkey consumed was measured. Whole, uncoagulated blood was collected from each animal at the end of the entire experimental procedure. PEth 16:0/18:1 and PEth 16:0/18:2 levels were analyzed by HPLC with tandem mass spectrometry, and the ethanol consumed during the preceding 14 days was measured. Combined PEth was the sum of the concentrations of both homologs.
Results
Our results show that (1) PEth accumulates in the blood of rhesus monkeys after ethanol consumption; (2) PEth homolog levels were correlated with the daily average ethanol intake during the 14‐day period immediately preceding blood collection; (3) the application of established human PEth 16:0/18:1 cutoff concentrations indicative of light social or no ethanol consumption (<20 ng/ml), moderate ethanol consumption (≥ 20 and < 200 ng/ml) and heavy ethanol consumption (≥ 200 ng/ml) predicted significantly different ethanol intake in these animals. PEth homologs were not detected in ethanol‐naïve controls.
Conclusions
This study confirms that PEth is a sensitive biomarker for ethanol consumption in rhesus macaque monkeys. This nonhuman primate model may prove useful in evaluating sources of variability previously shown to exist between ethanol consumption and PEth homolog levels among humans.
This novel study shows that PEth, a direct biomarker of ethanol intake, is present in the blood of Rhesus monkeys after consuming ethanol ad libitum; and that the levels of the two most abundant PEth homologs, PEth 16:0/18:1 and PEth 16:0/18:2, are detectable as a function of daily ethanol consumed. This pre‐clinical model provides a greater experimental control over ethanol dosing, which could help understand and interpret variability found in PEth in human blood samples.</description><identifier>ISSN: 0145-6008</identifier><identifier>ISSN: 1530-0277</identifier><identifier>EISSN: 1530-0277</identifier><identifier>DOI: 10.1111/acer.14584</identifier><identifier>PMID: 33616217</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Alcohol Drinking - blood ; Amino Acid Sequence ; Animal models ; Animals ; blood ; Central Nervous System Depressants - administration & dosage ; Conserved Sequence ; Drinking behavior ; Ethanol ; Ethanol - administration & dosage ; Glycerophospholipids - blood ; High-performance liquid chromatography ; Humans ; Macaca mulatta ; Male ; Mass spectroscopy ; Monkeys & apes ; phosphatidylethanol (PEth) ; phospholipase D (PLD) ; Phospholipase D - chemistry ; rhesus monkey</subject><ispartof>Alcoholism, clinical and experimental research, 2021-04, Vol.45 (4), p.689-696</ispartof><rights>2021 by the Research Society on Alcoholism</rights><rights>2021 by the Research Society on Alcoholism.</rights><rights>2021 Research Society on Alcoholism</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4484-47209f6c3ecba700c3e27afb662631005237e7f1181784418f2840767d3d71e3</citedby><cites>FETCH-LOGICAL-c4484-47209f6c3ecba700c3e27afb662631005237e7f1181784418f2840767d3d71e3</cites><orcidid>0000-0003-0285-1012 ; 0000-0002-0380-7219</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Facer.14584$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Facer.14584$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33616217$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lopez‐Cruzan, Marisa</creatorcontrib><creatorcontrib>Walter, Nicole A. R.</creatorcontrib><creatorcontrib>Sanchez, Jesus J.</creatorcontrib><creatorcontrib>Ginsburg, Brett C.</creatorcontrib><creatorcontrib>Koek, Wouter</creatorcontrib><creatorcontrib>Jimenez, Vanessa A.</creatorcontrib><creatorcontrib>Grant, Kathleen A.</creatorcontrib><creatorcontrib>Javors, Martin A.</creatorcontrib><title>Phosphatidylethanol in whole blood of rhesus monkeys correlates with ethanol consumption</title><title>Alcoholism, clinical and experimental research</title><addtitle>Alcohol Clin Exp Res</addtitle><description>Background
Phosphatidylethanol (PEth) homologs are ethanol metabolites used to identify and monitor alcohol drinking in humans. In this study, we measured levels of the 2 most abundant homologs, PEth 16:0/18:1 and PEth 16:0/18:2, in whole blood samples from rhesus macaque monkeys that drank ethanol daily ad libitum to assess the relationship between PEth levels and recent ethanol exposure in this animal model.
Methods
Blood samples were obtained from The Monkey Alcohol Tissue Research Resource. The monkeys were first induced to consume 4% (w/v) ethanol in water from a panel attached to their home cage. Then, monkeys were allowed to drink ethanol and water ad libitum 22 h daily for 12 months and the daily amount of ethanol each monkey consumed was measured. Whole, uncoagulated blood was collected from each animal at the end of the entire experimental procedure. PEth 16:0/18:1 and PEth 16:0/18:2 levels were analyzed by HPLC with tandem mass spectrometry, and the ethanol consumed during the preceding 14 days was measured. Combined PEth was the sum of the concentrations of both homologs.
Results
Our results show that (1) PEth accumulates in the blood of rhesus monkeys after ethanol consumption; (2) PEth homolog levels were correlated with the daily average ethanol intake during the 14‐day period immediately preceding blood collection; (3) the application of established human PEth 16:0/18:1 cutoff concentrations indicative of light social or no ethanol consumption (<20 ng/ml), moderate ethanol consumption (≥ 20 and < 200 ng/ml) and heavy ethanol consumption (≥ 200 ng/ml) predicted significantly different ethanol intake in these animals. PEth homologs were not detected in ethanol‐naïve controls.
Conclusions
This study confirms that PEth is a sensitive biomarker for ethanol consumption in rhesus macaque monkeys. This nonhuman primate model may prove useful in evaluating sources of variability previously shown to exist between ethanol consumption and PEth homolog levels among humans.
This novel study shows that PEth, a direct biomarker of ethanol intake, is present in the blood of Rhesus monkeys after consuming ethanol ad libitum; and that the levels of the two most abundant PEth homologs, PEth 16:0/18:1 and PEth 16:0/18:2, are detectable as a function of daily ethanol consumed. This pre‐clinical model provides a greater experimental control over ethanol dosing, which could help understand and interpret variability found in PEth in human blood samples.</description><subject>Alcohol Drinking - blood</subject><subject>Amino Acid Sequence</subject><subject>Animal models</subject><subject>Animals</subject><subject>blood</subject><subject>Central Nervous System Depressants - administration & dosage</subject><subject>Conserved Sequence</subject><subject>Drinking behavior</subject><subject>Ethanol</subject><subject>Ethanol - administration & dosage</subject><subject>Glycerophospholipids - blood</subject><subject>High-performance liquid chromatography</subject><subject>Humans</subject><subject>Macaca mulatta</subject><subject>Male</subject><subject>Mass spectroscopy</subject><subject>Monkeys & apes</subject><subject>phosphatidylethanol (PEth)</subject><subject>phospholipase D (PLD)</subject><subject>Phospholipase D - chemistry</subject><subject>rhesus monkey</subject><issn>0145-6008</issn><issn>1530-0277</issn><issn>1530-0277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2LFDEQhoMo7rh68QdIwIsIvVY-OslchGVYP2BBkT14C5l0tZ013RmTbof592ad3UU9mEMlVJ48VHgJec7gjNX1xnnMZ0y2Rj4gK9YKaIBr_ZCsoDYbBWBOyJNSrgFAGqUekxMhFFOc6RX5-nlIZTe4OXSHiPPgphRpmOh-SBHpNqbU0dTTPGBZCh3T9B0PhfqUM0Y3Y6H7MA_07qFPU1nG3RzS9JQ86l0s-Ox2PyVX7y6uNh-ay0_vP27OLxsvpZGN1BzWvfIC_dZpgHrg2vVbpbgSDKDlQqPuGTNMGymZ6bmRoJXuRKcZilPy9qjdLdsRO4_TnF20uxxGlw82uWD_vpnCYL-ln9awFoxpq-DVrSCnHwuW2Y6heIzRTZiWYrlcc27WtVT05T_odVryVH9necs0F6KFdaVeHymfUykZ-_thGNibvOxNXvZ3XhV-8ef49-hdQBVgR2AfIh7-o7Lnm4svR-kvpoCg9A</recordid><startdate>202104</startdate><enddate>202104</enddate><creator>Lopez‐Cruzan, Marisa</creator><creator>Walter, Nicole A. R.</creator><creator>Sanchez, Jesus J.</creator><creator>Ginsburg, Brett C.</creator><creator>Koek, Wouter</creator><creator>Jimenez, Vanessa A.</creator><creator>Grant, Kathleen A.</creator><creator>Javors, Martin A.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>K7.</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0285-1012</orcidid><orcidid>https://orcid.org/0000-0002-0380-7219</orcidid></search><sort><creationdate>202104</creationdate><title>Phosphatidylethanol in whole blood of rhesus monkeys correlates with ethanol consumption</title><author>Lopez‐Cruzan, Marisa ; Walter, Nicole A. R. ; Sanchez, Jesus J. ; Ginsburg, Brett C. ; Koek, Wouter ; Jimenez, Vanessa A. ; Grant, Kathleen A. ; Javors, Martin A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4484-47209f6c3ecba700c3e27afb662631005237e7f1181784418f2840767d3d71e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alcohol Drinking - blood</topic><topic>Amino Acid Sequence</topic><topic>Animal models</topic><topic>Animals</topic><topic>blood</topic><topic>Central Nervous System Depressants - administration & dosage</topic><topic>Conserved Sequence</topic><topic>Drinking behavior</topic><topic>Ethanol</topic><topic>Ethanol - administration & dosage</topic><topic>Glycerophospholipids - blood</topic><topic>High-performance liquid chromatography</topic><topic>Humans</topic><topic>Macaca mulatta</topic><topic>Male</topic><topic>Mass spectroscopy</topic><topic>Monkeys & apes</topic><topic>phosphatidylethanol (PEth)</topic><topic>phospholipase D (PLD)</topic><topic>Phospholipase D - chemistry</topic><topic>rhesus monkey</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lopez‐Cruzan, Marisa</creatorcontrib><creatorcontrib>Walter, Nicole A. R.</creatorcontrib><creatorcontrib>Sanchez, Jesus J.</creatorcontrib><creatorcontrib>Ginsburg, Brett C.</creatorcontrib><creatorcontrib>Koek, Wouter</creatorcontrib><creatorcontrib>Jimenez, Vanessa A.</creatorcontrib><creatorcontrib>Grant, Kathleen A.</creatorcontrib><creatorcontrib>Javors, Martin A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Criminal Justice (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Alcoholism, clinical and experimental research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lopez‐Cruzan, Marisa</au><au>Walter, Nicole A. R.</au><au>Sanchez, Jesus J.</au><au>Ginsburg, Brett C.</au><au>Koek, Wouter</au><au>Jimenez, Vanessa A.</au><au>Grant, Kathleen A.</au><au>Javors, Martin A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phosphatidylethanol in whole blood of rhesus monkeys correlates with ethanol consumption</atitle><jtitle>Alcoholism, clinical and experimental research</jtitle><addtitle>Alcohol Clin Exp Res</addtitle><date>2021-04</date><risdate>2021</risdate><volume>45</volume><issue>4</issue><spage>689</spage><epage>696</epage><pages>689-696</pages><issn>0145-6008</issn><issn>1530-0277</issn><eissn>1530-0277</eissn><abstract>Background
Phosphatidylethanol (PEth) homologs are ethanol metabolites used to identify and monitor alcohol drinking in humans. In this study, we measured levels of the 2 most abundant homologs, PEth 16:0/18:1 and PEth 16:0/18:2, in whole blood samples from rhesus macaque monkeys that drank ethanol daily ad libitum to assess the relationship between PEth levels and recent ethanol exposure in this animal model.
Methods
Blood samples were obtained from The Monkey Alcohol Tissue Research Resource. The monkeys were first induced to consume 4% (w/v) ethanol in water from a panel attached to their home cage. Then, monkeys were allowed to drink ethanol and water ad libitum 22 h daily for 12 months and the daily amount of ethanol each monkey consumed was measured. Whole, uncoagulated blood was collected from each animal at the end of the entire experimental procedure. PEth 16:0/18:1 and PEth 16:0/18:2 levels were analyzed by HPLC with tandem mass spectrometry, and the ethanol consumed during the preceding 14 days was measured. Combined PEth was the sum of the concentrations of both homologs.
Results
Our results show that (1) PEth accumulates in the blood of rhesus monkeys after ethanol consumption; (2) PEth homolog levels were correlated with the daily average ethanol intake during the 14‐day period immediately preceding blood collection; (3) the application of established human PEth 16:0/18:1 cutoff concentrations indicative of light social or no ethanol consumption (<20 ng/ml), moderate ethanol consumption (≥ 20 and < 200 ng/ml) and heavy ethanol consumption (≥ 200 ng/ml) predicted significantly different ethanol intake in these animals. PEth homologs were not detected in ethanol‐naïve controls.
Conclusions
This study confirms that PEth is a sensitive biomarker for ethanol consumption in rhesus macaque monkeys. This nonhuman primate model may prove useful in evaluating sources of variability previously shown to exist between ethanol consumption and PEth homolog levels among humans.
This novel study shows that PEth, a direct biomarker of ethanol intake, is present in the blood of Rhesus monkeys after consuming ethanol ad libitum; and that the levels of the two most abundant PEth homologs, PEth 16:0/18:1 and PEth 16:0/18:2, are detectable as a function of daily ethanol consumed. This pre‐clinical model provides a greater experimental control over ethanol dosing, which could help understand and interpret variability found in PEth in human blood samples.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33616217</pmid><doi>10.1111/acer.14584</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-0285-1012</orcidid><orcidid>https://orcid.org/0000-0002-0380-7219</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Alcoholism, clinical and experimental research, 2021-04, Vol.45 (4), p.689-696 |
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| source | MEDLINE; Access via Wiley Online Library |
| subjects | Alcohol Drinking - blood Amino Acid Sequence Animal models Animals blood Central Nervous System Depressants - administration & dosage Conserved Sequence Drinking behavior Ethanol Ethanol - administration & dosage Glycerophospholipids - blood High-performance liquid chromatography Humans Macaca mulatta Male Mass spectroscopy Monkeys & apes phosphatidylethanol (PEth) phospholipase D (PLD) Phospholipase D - chemistry rhesus monkey |
| title | Phosphatidylethanol in whole blood of rhesus monkeys correlates with ethanol consumption |
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