Potential biomarkers and metabolomics of acetaminophen-induced liver injury during alcohol consumption: A preclinical investigation on C57/BL6 mice
The toxic effects of alcohol consumption on population health are significant worldwide and the synergistic toxic effects of concurrent intake of Acetaminophen and alcohol is of clinical concern. The understanding of molecular mechanisms beneath such synergism and acute toxicity may be enhanced thro...
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| Veröffentlicht in: | Toxicology and applied pharmacology 2023-04, Vol.465, p.116451-116451, Article 116451 |
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| creator | Jaber, Malak A. Ghanim, Bayan Y. Al-Natour, Mohammad Arqoub, Duaa Abu Abdallah, Qasem Abdelrazig, Salah Alkrad, Jamal Alyousse Kim, Dong-Hyun Qinna, Nidal A. |
| description | The toxic effects of alcohol consumption on population health are significant worldwide and the synergistic toxic effects of concurrent intake of Acetaminophen and alcohol is of clinical concern. The understanding of molecular mechanisms beneath such synergism and acute toxicity may be enhanced through assessing underlying metabolomics changes. The molecular toxic activities of the model hereby, is assessed though metabolomics profile with a view to identifying metabolomics targets which could aid in the management of drug-alcohol interactions. In vivo exposure of C57/BL6 mice to APAP (70 mg/kg), single dose of ethanol (6 g/kg of 40%) and APAP after alcohol consumption was employed. Plasma samples were prepared and subjected to biphasic extraction for complete LC-MS profiling, and tandem mass MS2 analysis. Among the detected ions, 174 ions had significant (VIP scores >1 and FDR |
| doi_str_mv | 10.1016/j.taap.2023.116451 |
| format | Article |
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[Display omitted]
•Non-targeted metabolomics analysis using LC-MS provides a snapshot on biomolecules.•More than a hundred metabolites and mass ions are altered after EtOH exposure.•Several metabolism pathways are affected by concurrent use of EtOH and paracetamol.•Nucleotide and amino acid metabolism and synthesis are influenced by EtOH toxicity.•Bioenergetics of the hepatic cell; TCA and Krebs cycle are also inhibited.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2023.116451</identifier><identifier>PMID: 36894070</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acetaminophen - toxicity ; Alcohol Drinking - adverse effects ; Amino Acids - metabolism ; Animals ; Biomarkers ; Chemical and Drug Induced Liver Injury - etiology ; Chemical and Drug Induced Liver Injury - metabolism ; Chemical and Drug Induced Liver Injury, Chronic - metabolism ; Krebs Cycle ; Liver ; Metabolism ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Non-targeted LC-MS Metabolomics ; Oxidative Stress ; TCA Cycle</subject><ispartof>Toxicology and applied pharmacology, 2023-04, Vol.465, p.116451-116451, Article 116451</ispartof><rights>2023 Elsevier Inc.</rights><rights>Copyright © 2023 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-bfc0b5f8b9a56d2db5890b6baa7e4dc07d0990b606b55db81c6ad67e277cfca23</citedby><cites>FETCH-LOGICAL-c356t-bfc0b5f8b9a56d2db5890b6baa7e4dc07d0990b606b55db81c6ad67e277cfca23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.taap.2023.116451$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36894070$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jaber, Malak A.</creatorcontrib><creatorcontrib>Ghanim, Bayan Y.</creatorcontrib><creatorcontrib>Al-Natour, Mohammad</creatorcontrib><creatorcontrib>Arqoub, Duaa Abu</creatorcontrib><creatorcontrib>Abdallah, Qasem</creatorcontrib><creatorcontrib>Abdelrazig, Salah</creatorcontrib><creatorcontrib>Alkrad, Jamal Alyousse</creatorcontrib><creatorcontrib>Kim, Dong-Hyun</creatorcontrib><creatorcontrib>Qinna, Nidal A.</creatorcontrib><title>Potential biomarkers and metabolomics of acetaminophen-induced liver injury during alcohol consumption: A preclinical investigation on C57/BL6 mice</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>The toxic effects of alcohol consumption on population health are significant worldwide and the synergistic toxic effects of concurrent intake of Acetaminophen and alcohol is of clinical concern. The understanding of molecular mechanisms beneath such synergism and acute toxicity may be enhanced through assessing underlying metabolomics changes. The molecular toxic activities of the model hereby, is assessed though metabolomics profile with a view to identifying metabolomics targets which could aid in the management of drug-alcohol interactions. In vivo exposure of C57/BL6 mice to APAP (70 mg/kg), single dose of ethanol (6 g/kg of 40%) and APAP after alcohol consumption was employed. Plasma samples were prepared and subjected to biphasic extraction for complete LC-MS profiling, and tandem mass MS2 analysis. Among the detected ions, 174 ions had significant (VIP scores >1 and FDR <0.05) changes between groups and were selected as potential biomarkers and significant variables. The presented metabolomics approach highlighted several affected metabolic pathways, including nucleotide and amino acid metabolism; aminoacyl-tRNA biosynthesis as well as bioenergetics of TCA and Krebs cycle. The impact of APAP on the concurrent administration of alcohol showed great biological interactions in the vital ATP and amino acid producing processes. The metabolomics changes show distinct metabolites which are altered to alcohol-APAP consumption while presenting several unneglectable risks on the vitality of metabolites and cellular molecules which shall be concerned.
[Display omitted]
•Non-targeted metabolomics analysis using LC-MS provides a snapshot on biomolecules.•More than a hundred metabolites and mass ions are altered after EtOH exposure.•Several metabolism pathways are affected by concurrent use of EtOH and paracetamol.•Nucleotide and amino acid metabolism and synthesis are influenced by EtOH toxicity.•Bioenergetics of the hepatic cell; TCA and Krebs cycle are also inhibited.</description><subject>Acetaminophen - toxicity</subject><subject>Alcohol Drinking - adverse effects</subject><subject>Amino Acids - metabolism</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Chemical and Drug Induced Liver Injury - etiology</subject><subject>Chemical and Drug Induced Liver Injury - metabolism</subject><subject>Chemical and Drug Induced Liver Injury, Chronic - metabolism</subject><subject>Krebs Cycle</subject><subject>Liver</subject><subject>Metabolism</subject><subject>Metabolomics</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Non-targeted LC-MS Metabolomics</subject><subject>Oxidative Stress</subject><subject>TCA Cycle</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU2LFDEQDaK4s6t_wIPk6KVnK_2R7hYv66CrMKAHBW8hH9W7NXYnbdI9sL_DP2yGWT0KBQWVV-9V3mPslYCtACGvD9tF63lbQllthZB1I56wjYBeFlBV1VO2AahFAdD9uGCXKR0AoK9r8ZxdVLLra2hhw35_DQv6hfTIDYVJx58YE9fe8QkXbcIYJrKJh4FrmwcT-TDfoy_Iu9Wi4yMdMXLyhzU-cLdG8ndcjzbch5Hb4NM6zQsF_5bf8DmiHcmTzVrkj5gWutOnR55r17TX7_eSZzV8wZ4Nekz48rFfse8fP3zbfSr2X24_7272ha0auRRmsGCaoTO9bqQrnWm6How0WrdYOwutg_40AGmaxplOWKmdbLFsWztYXVZX7M2Zd47h15rvURMli-OoPYY1qbLtJPRZS2ZoeYbaGFKKOKg5UnbrQQlQpzDUQZ3CUKcw1DmMvPT6kX81E7p_K3_dz4B3ZwDmXx4Jo0qW0GdfKXu1KBfof_x_ADQ8nrU</recordid><startdate>20230415</startdate><enddate>20230415</enddate><creator>Jaber, Malak A.</creator><creator>Ghanim, Bayan Y.</creator><creator>Al-Natour, Mohammad</creator><creator>Arqoub, Duaa Abu</creator><creator>Abdallah, Qasem</creator><creator>Abdelrazig, Salah</creator><creator>Alkrad, Jamal Alyousse</creator><creator>Kim, Dong-Hyun</creator><creator>Qinna, Nidal A.</creator><general>Elsevier 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>7X8</scope></search><sort><creationdate>20230415</creationdate><title>Potential biomarkers and metabolomics of acetaminophen-induced liver injury during alcohol consumption: A preclinical investigation on C57/BL6 mice</title><author>Jaber, Malak A. ; Ghanim, Bayan Y. ; Al-Natour, Mohammad ; Arqoub, Duaa Abu ; Abdallah, Qasem ; Abdelrazig, Salah ; Alkrad, Jamal Alyousse ; Kim, Dong-Hyun ; Qinna, Nidal A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-bfc0b5f8b9a56d2db5890b6baa7e4dc07d0990b606b55db81c6ad67e277cfca23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Acetaminophen - toxicity</topic><topic>Alcohol Drinking - adverse effects</topic><topic>Amino Acids - metabolism</topic><topic>Animals</topic><topic>Biomarkers</topic><topic>Chemical and Drug Induced Liver Injury - etiology</topic><topic>Chemical and Drug Induced Liver Injury - metabolism</topic><topic>Chemical and Drug Induced Liver Injury, Chronic - metabolism</topic><topic>Krebs Cycle</topic><topic>Liver</topic><topic>Metabolism</topic><topic>Metabolomics</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Non-targeted LC-MS Metabolomics</topic><topic>Oxidative Stress</topic><topic>TCA Cycle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jaber, Malak A.</creatorcontrib><creatorcontrib>Ghanim, Bayan Y.</creatorcontrib><creatorcontrib>Al-Natour, Mohammad</creatorcontrib><creatorcontrib>Arqoub, Duaa Abu</creatorcontrib><creatorcontrib>Abdallah, Qasem</creatorcontrib><creatorcontrib>Abdelrazig, Salah</creatorcontrib><creatorcontrib>Alkrad, Jamal Alyousse</creatorcontrib><creatorcontrib>Kim, Dong-Hyun</creatorcontrib><creatorcontrib>Qinna, Nidal 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>MEDLINE - Academic</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jaber, Malak A.</au><au>Ghanim, Bayan Y.</au><au>Al-Natour, Mohammad</au><au>Arqoub, Duaa Abu</au><au>Abdallah, Qasem</au><au>Abdelrazig, Salah</au><au>Alkrad, Jamal Alyousse</au><au>Kim, Dong-Hyun</au><au>Qinna, Nidal A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potential biomarkers and metabolomics of acetaminophen-induced liver injury during alcohol consumption: A preclinical investigation on C57/BL6 mice</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2023-04-15</date><risdate>2023</risdate><volume>465</volume><spage>116451</spage><epage>116451</epage><pages>116451-116451</pages><artnum>116451</artnum><issn>0041-008X</issn><eissn>1096-0333</eissn><abstract>The toxic effects of alcohol consumption on population health are significant worldwide and the synergistic toxic effects of concurrent intake of Acetaminophen and alcohol is of clinical concern. The understanding of molecular mechanisms beneath such synergism and acute toxicity may be enhanced through assessing underlying metabolomics changes. The molecular toxic activities of the model hereby, is assessed though metabolomics profile with a view to identifying metabolomics targets which could aid in the management of drug-alcohol interactions. In vivo exposure of C57/BL6 mice to APAP (70 mg/kg), single dose of ethanol (6 g/kg of 40%) and APAP after alcohol consumption was employed. Plasma samples were prepared and subjected to biphasic extraction for complete LC-MS profiling, and tandem mass MS2 analysis. Among the detected ions, 174 ions had significant (VIP scores >1 and FDR <0.05) changes between groups and were selected as potential biomarkers and significant variables. The presented metabolomics approach highlighted several affected metabolic pathways, including nucleotide and amino acid metabolism; aminoacyl-tRNA biosynthesis as well as bioenergetics of TCA and Krebs cycle. The impact of APAP on the concurrent administration of alcohol showed great biological interactions in the vital ATP and amino acid producing processes. The metabolomics changes show distinct metabolites which are altered to alcohol-APAP consumption while presenting several unneglectable risks on the vitality of metabolites and cellular molecules which shall be concerned.
[Display omitted]
•Non-targeted metabolomics analysis using LC-MS provides a snapshot on biomolecules.•More than a hundred metabolites and mass ions are altered after EtOH exposure.•Several metabolism pathways are affected by concurrent use of EtOH and paracetamol.•Nucleotide and amino acid metabolism and synthesis are influenced by EtOH toxicity.•Bioenergetics of the hepatic cell; TCA and Krebs cycle are also inhibited.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>36894070</pmid><doi>10.1016/j.taap.2023.116451</doi><tpages>1</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0041-008X |
| ispartof | Toxicology and applied pharmacology, 2023-04, Vol.465, p.116451-116451, Article 116451 |
| issn | 0041-008X 1096-0333 |
| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Acetaminophen - toxicity Alcohol Drinking - adverse effects Amino Acids - metabolism Animals Biomarkers Chemical and Drug Induced Liver Injury - etiology Chemical and Drug Induced Liver Injury - metabolism Chemical and Drug Induced Liver Injury, Chronic - metabolism Krebs Cycle Liver Metabolism Metabolomics Mice Mice, Inbred C57BL Non-targeted LC-MS Metabolomics Oxidative Stress TCA Cycle |
| title | Potential biomarkers and metabolomics of acetaminophen-induced liver injury during alcohol consumption: A preclinical investigation on C57/BL6 mice |
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