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 pathophysiolo-gies of liver injury.Levels of CES1 and DPP-Ⅳ can be used to identify liver damage itself and the inflam-matory state,respectively.While the levels of the conventional serological biomarkers alkaline phosphatase(ALP),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were all con-comitantly 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 y-glutamyl transpeptidase(y-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 with-out 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 intra-hepatic 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.

Qiusha Pan;Peifang Song;Zhenhua Ni;Xingkai Qian;Anqi Wang;Liwei Zou;Yong Liu;Ping Wang;Weidong Zhang;Hong Ma;Ling Yang

Center for Systems Pharmacokinetics,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China;School of Life and Pharmaceutical Sciences,Dalian University of Technology,Dalian 116024,China;Shanghai Institute of Acupuncture and Meridian,Shanghai 200030,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

工程（英文）

[1]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)[J].工程（英文）,2022(12):153-165

Peptidase,mutuality,pathophysiolo,comitantly,ascended,Pai,QFPDD

Assessment,Tracking,Process,Liver,Specific,Injury,by,Residual,Tissue,Activity,Carboxylesterase,Dipeptidyl,Accurately,assessing,tracking,progression,liver,injury,remains,major,challenge,field,research,Here,took,retrospective,validation,approach,built,between,serum,biomarkers,characterize,bile,duct,cells,caused,naphthyl,isothiocyanate,ANIT,We,found,that,carboxylesterase,CES1,intrahepatic,dipeptidyl,DPP,IV,extrahepatic,can,reflect,gies,Levels,identify,itself,state,respectively,While,levels,conventional,serological,alkaline,phosphatase,ALP,alanine,aminotransferase,ALT,aspartate,AST,were,elevated,tissues,after,induced,acids,decreased,increased,Although,glutamyl,transpeptidase,GT,changed,opposite,direction,duration,was,much,shorter,than,quickly,restored,normal,Therefore,among,abovementioned,only,made,possible,specifically,determine,whether,destroyed,damaged,out,interference,from,inflammation,also,enabled,accurate,assessment,anti,cholestasis,effects,ursodeoxycholic,UDCA,single,component,Qing,Fei,Du,Decoction,multi,both,attenuated,more,promoting,excretion,but,showed,relatively,weaker,inflammatory,whereas,effective,blocking,repairing,Our,data,highlights,potential,combined,evaluation,application,allows,differentiation

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