Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol

Abstract Tramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear. Limited literature available indicates the change of proteomic profile after chronic e...

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Autores principales:	Shukun Jiang, Guojie Liu, Huiya Yuan, Enyu Xu, Wei Xia, Xiaoyu Zhang, Junting Liu, Lina Gao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc95a248587f46d2af5358b00d95bcc3
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spelling	oai:doaj.org-article:cc95a248587f46d2af5358b00d95bcc32021-12-02T14:12:41ZChanges on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol10.1038/s41598-021-81109-72045-2322https://doaj.org/article/cc95a248587f46d2af5358b00d95bcc32021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81109-7https://doaj.org/toc/2045-2322Abstract Tramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear. Limited literature available indicates the change of proteomic profile after chronic exposure to tramadol. In this study, we analyzed the proteomic and metabolomic profile by TMT-labeled quantitative proteomics and untargeted metabolomics between the tramadol and the control group. Proteomic analysis revealed 31 differential expressed serum proteins (9 increased and 22 decreased) in tramadol-treated mice (oral, 50 mg/kg, 5 weeks) as compared with the control ones. Bioinformatics analysis showed that the dysregulated proteins mainly included: enzyme inhibitor-associated proteins (i.e. apolipoprotein C-III (Apoc-III), alpha-1-antitrypsin 1–2 (Serpina 1b), apolipoprotein C-II (Apoc-II), plasma protease C1 inhibitor, inter-alpha-trypsin inhibitor heavy chain H3 (itih3)); mitochondria-related proteins (i.e. 14-3-3 protein zeta/delta (YWHAZ)); cytoskeleton proteins (i.e. tubulin alpha-4A chain (TUBA4A), vinculin (Vcl)). And we found that the differential expressed proteins mainly involved in the pathway of the protein digestion and absorption. Metabolomics analysis revealed that differential expressed metabolites mainly involved in protein ingestion and absorption, fatty acid biosynthesis, steroid hormone biosynthesis and bile secretion. Our overall findings revealed that chronic exposure to tramadol changed the proteomic and metabolomic profile of mice. Moreover, integrated proteomic and metabolomic revealed that the protein digestion and absorption is the common enrichment KEGG pathway. Thus, the combination of proteomics and metabolomics opens new avenues for the research of the molecular mechanisms of tramadol toxicity.Shukun JiangGuojie LiuHuiya YuanEnyu XuWei XiaXiaoyu ZhangJunting LiuLina GaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shukun Jiang Guojie Liu Huiya Yuan Enyu Xu Wei Xia Xiaoyu Zhang Junting Liu Lina Gao Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol
description	Abstract Tramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear. Limited literature available indicates the change of proteomic profile after chronic exposure to tramadol. In this study, we analyzed the proteomic and metabolomic profile by TMT-labeled quantitative proteomics and untargeted metabolomics between the tramadol and the control group. Proteomic analysis revealed 31 differential expressed serum proteins (9 increased and 22 decreased) in tramadol-treated mice (oral, 50 mg/kg, 5 weeks) as compared with the control ones. Bioinformatics analysis showed that the dysregulated proteins mainly included: enzyme inhibitor-associated proteins (i.e. apolipoprotein C-III (Apoc-III), alpha-1-antitrypsin 1–2 (Serpina 1b), apolipoprotein C-II (Apoc-II), plasma protease C1 inhibitor, inter-alpha-trypsin inhibitor heavy chain H3 (itih3)); mitochondria-related proteins (i.e. 14-3-3 protein zeta/delta (YWHAZ)); cytoskeleton proteins (i.e. tubulin alpha-4A chain (TUBA4A), vinculin (Vcl)). And we found that the differential expressed proteins mainly involved in the pathway of the protein digestion and absorption. Metabolomics analysis revealed that differential expressed metabolites mainly involved in protein ingestion and absorption, fatty acid biosynthesis, steroid hormone biosynthesis and bile secretion. Our overall findings revealed that chronic exposure to tramadol changed the proteomic and metabolomic profile of mice. Moreover, integrated proteomic and metabolomic revealed that the protein digestion and absorption is the common enrichment KEGG pathway. Thus, the combination of proteomics and metabolomics opens new avenues for the research of the molecular mechanisms of tramadol toxicity.
format	article
author	Shukun Jiang Guojie Liu Huiya Yuan Enyu Xu Wei Xia Xiaoyu Zhang Junting Liu Lina Gao
author_facet	Shukun Jiang Guojie Liu Huiya Yuan Enyu Xu Wei Xia Xiaoyu Zhang Junting Liu Lina Gao
author_sort	Shukun Jiang
title	Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol
title_short	Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol
title_full	Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol
title_fullStr	Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol
title_full_unstemmed	Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol
title_sort	changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cc95a248587f46d2af5358b00d95bcc3
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_version_	1718391811963092992

Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol

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