Accurate Assessment and Tracking the Process of Liver-Specific Injury by the Residual Tissue Activity of Carboxylesterase 1 and Dipeptidyl Peptidase 4

Accurately assessing and tracking the progression of liver-specific injury remains a major challenge in the field of biomarker research. Here, we took a retrospective validation approach built on the mutuality between serum and tissue biomarkers to characterize the liver-specific damage of bile duct...

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Main Authors: Qiusha Pan, Peifang Song, Zhenhua Ni, Xingkai Qian, Anqi Wang, Liwei Zou, Yong Liu, Ping Wang, Weidong Zhang, Hong Ma, Ling Yang
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Engineering
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2095809921005270
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author Qiusha Pan
Peifang Song
Zhenhua Ni
Xingkai Qian
Anqi Wang
Liwei Zou
Yong Liu
Ping Wang
Weidong Zhang
Hong Ma
Ling Yang
author_facet Qiusha Pan
Peifang Song
Zhenhua Ni
Xingkai Qian
Anqi Wang
Liwei Zou
Yong Liu
Ping Wang
Weidong Zhang
Hong Ma
Ling Yang
author_sort Qiusha Pan
collection DOAJ
description Accurately assessing and tracking the progression of liver-specific injury remains a major challenge in the field of biomarker research. Here, we took a retrospective validation approach built on the mutuality between serum and tissue biomarkers to characterize the liver-specific damage of bile duct cells caused by α-naphthyl isothiocyanate (ANIT). We found that carboxylesterase 1 (CES1), as an intrahepatic marker, and dipeptidyl peptidase 4 (DPP-IV), as an extrahepatic marker, can reflect the different pathophysiologies of liver injury. Levels of CES1 and DPP-IV can be used to identify liver damage itself and the inflammatory state, respectively. While the levels of the conventional serological biomarkers alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were all concomitantly elevated in serum and tissues after ANIT-induced injury, the levels of bile acids decreased in bile, increased in serum, and ascended in intrahepatic tissue. Although the level of γ-glutamyl transpeptidase (γ-GT) changed in an opposite direction, the duration was much shorter than that of CES1 and was quickly restored to normal levels. Therefore, among the abovementioned biomarkers, only CES1 made it possible to specifically determine whether the liver cells were destroyed or damaged without interference from inflammation. CES1 also enabled accurate assessment of the anti-cholestasis effects of ursodeoxycholic acid (UDCA; single component) and Qing Fei Pai Du Decoction (QFPDD; multi-component). We found that both QFPDD and UDCA attenuated ANIT-induced liver damage. UDCA was more potent in promoting bile excretion but showed relatively weaker anti-injury and anti-inflammatory effects than QFPDD, whereas QFPDD was more effective in blocking liver inflammation and repairing liver damage. Our data highlights the potential of the combined use of CES1 (as an intrahepatic marker of liver damage) and DPP-IV (as an extrahepatic marker of inflammation) for the accurate evaluation and tracking of liver-specific injury—an application that allows for the differentiation of liver damage and inflammatory liver injury.
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spelling doaj.art-36e96093e44848328990eb579e44c2ee2023-03-09T04:13:16ZengElsevierEngineering2095-80992022-12-0119153165Accurate Assessment and Tracking the Process of Liver-Specific Injury by the Residual Tissue Activity of Carboxylesterase 1 and Dipeptidyl Peptidase 4Qiusha Pan0Peifang Song1Zhenhua Ni2Xingkai Qian3Anqi Wang4Liwei Zou5Yong Liu6Ping Wang7Weidong Zhang8Hong Ma9Ling Yang10Center for Systems Pharmacokinetics, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, ChinaCenter for Systems Pharmacokinetics, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaCenter for Systems Pharmacokinetics, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, ChinaCenter for Systems Pharmacokinetics, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaCenter for Systems Pharmacokinetics, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaCenter for Systems Pharmacokinetics, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Life and Pharmaceutical Sciences, Dalian University of Technology, Dalian 116024, ChinaCenter for Systems Pharmacokinetics, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaCenter for Systems Pharmacokinetics, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaShanghai Institute of Acupuncture and Meridian, Shanghai 200030, China; Corresponding authors.Center for Systems Pharmacokinetics, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China; Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China; Corresponding authors.Accurately assessing and tracking the progression of liver-specific injury remains a major challenge in the field of biomarker research. Here, we took a retrospective validation approach built on the mutuality between serum and tissue biomarkers to characterize the liver-specific damage of bile duct cells caused by α-naphthyl isothiocyanate (ANIT). We found that carboxylesterase 1 (CES1), as an intrahepatic marker, and dipeptidyl peptidase 4 (DPP-IV), as an extrahepatic marker, can reflect the different pathophysiologies of liver injury. Levels of CES1 and DPP-IV can be used to identify liver damage itself and the inflammatory state, respectively. While the levels of the conventional serological biomarkers alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were all concomitantly elevated in serum and tissues after ANIT-induced injury, the levels of bile acids decreased in bile, increased in serum, and ascended in intrahepatic tissue. Although the level of γ-glutamyl transpeptidase (γ-GT) changed in an opposite direction, the duration was much shorter than that of CES1 and was quickly restored to normal levels. Therefore, among the abovementioned biomarkers, only CES1 made it possible to specifically determine whether the liver cells were destroyed or damaged without interference from inflammation. CES1 also enabled accurate assessment of the anti-cholestasis effects of ursodeoxycholic acid (UDCA; single component) and Qing Fei Pai Du Decoction (QFPDD; multi-component). We found that both QFPDD and UDCA attenuated ANIT-induced liver damage. UDCA was more potent in promoting bile excretion but showed relatively weaker anti-injury and anti-inflammatory effects than QFPDD, whereas QFPDD was more effective in blocking liver inflammation and repairing liver damage. Our data highlights the potential of the combined use of CES1 (as an intrahepatic marker of liver damage) and DPP-IV (as an extrahepatic marker of inflammation) for the accurate evaluation and tracking of liver-specific injury—an application that allows for the differentiation of liver damage and inflammatory liver injury.http://www.sciencedirect.com/science/article/pii/S2095809921005270Carboxylesterase 1Dipeptidyl peptidase 4Liver injuryValidation tracking
spellingShingle Qiusha Pan
Peifang Song
Zhenhua Ni
Xingkai Qian
Anqi Wang
Liwei Zou
Yong Liu
Ping Wang
Weidong Zhang
Hong Ma
Ling Yang
Accurate Assessment and Tracking the Process of Liver-Specific Injury by the Residual Tissue Activity of Carboxylesterase 1 and Dipeptidyl Peptidase 4
Engineering
Carboxylesterase 1
Dipeptidyl peptidase 4
Liver injury
Validation tracking
title Accurate Assessment and Tracking the Process of Liver-Specific Injury by the Residual Tissue Activity of Carboxylesterase 1 and Dipeptidyl Peptidase 4
title_full Accurate Assessment and Tracking the Process of Liver-Specific Injury by the Residual Tissue Activity of Carboxylesterase 1 and Dipeptidyl Peptidase 4
title_fullStr Accurate Assessment and Tracking the Process of Liver-Specific Injury by the Residual Tissue Activity of Carboxylesterase 1 and Dipeptidyl Peptidase 4
title_full_unstemmed Accurate Assessment and Tracking the Process of Liver-Specific Injury by the Residual Tissue Activity of Carboxylesterase 1 and Dipeptidyl Peptidase 4
title_short Accurate Assessment and Tracking the Process of Liver-Specific Injury by the Residual Tissue Activity of Carboxylesterase 1 and Dipeptidyl Peptidase 4
title_sort accurate assessment and tracking the process of liver specific injury by the residual tissue activity of carboxylesterase 1 and dipeptidyl peptidase 4
topic Carboxylesterase 1
Dipeptidyl peptidase 4
Liver injury
Validation tracking
url http://www.sciencedirect.com/science/article/pii/S2095809921005270
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