{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:06:35Z","timestamp":1792047995404,"version":"4.4.0"},"reference-count":41,"publisher":"American Chemical Society (ACS)","issue":"31","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004504","name":"Lietuvos Mokslo Taryba","doi-asserted-by":"publisher","award":["S-LU-24-12"],"award-info":[{"award-number":["S-LU-24-12"]}],"id":[{"id":"10.13039\/501100004504","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This study presents a rapid method for evaluating cholinesterase (ChE) activity using an amperometric choline biosensor based on an enzymatic membrane incorporating choline oxidase (ChOx) and a selectivity-providing acetylated cellulose layer. The developed biosensor shows a linear response range of 5\u2013500 \u03bcM for choline with a sensitivity of 32.2 \u00b1 0.3 \u03bcA\/(mM cm2), enabling the determination of choline in serum. The biosensor was also adapted for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) determination, achieving LODs of 0.003 and 0.005 U\/ml, respectively, with a linear range up to 0.5 U\/ml. Notably, the biosensor retains 88% of its initial sensitivity after 28 days of use. Two experimental rat nephropathy models were investigated: mild nephropathy induced by folic acid and advanced nephropathy induced by doxorubicin. A strong correlation between the proposed biosensor and colorimetric analysis was observed in rat serum samples (R2 = 0.988 for ChE; R2 = 0.979 for BChE), confirming its reliability and suitability. Biochemical parameter analysis of rat serum samples revealed a positive correlation between total protein levels and ChE\/BChE activity, and a negative correlation between C-reactive protein, ALT, and TBK-AP levels and ChE\/BChE activity. Furthermore, ChE and BChE activity was closely associated with nephropathy severity markers, including serum creatinine and urea concentrations. Increasing nephropathy severity was associated with a progressive decrease in cholinesterase activity. These findings highlight ChE activity as a potential indicator of nephropathy progression as well as hepatotoxicity and demonstrate the applicability of the proposed choline biosensors as accurate and efficient tools for wide-profile point-of-care biochemical analysis.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c01440","type":"journal-article","created":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T19:53:47Z","timestamp":1783886027000},"page":"22771-22780","source":"Crossref","is-referenced-by-count":1,"title":["Electrochemical\nBiosensor-Based Evaluation of Cholinergic\nBiomarkers in Experimental Nephropathy"],"prefix":"10.1021","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8484-8150","authenticated-orcid":true,"given":"Marius","family":"Butkevicius","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, Life Sciences Center Vilnius University , , Sauletekio Av. 7 , ,","place":["Vilnius, Lithuania, LT- 10257"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3707-9392","authenticated-orcid":true,"given":"Ieva","family":"Sakinyte-Urbikiene","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Life Sciences Center Vilnius University , , Sauletekio Av. 7 , ,","place":["Vilnius, Lithuania, LT- 10257"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Seniuk","sequence":"additional","affiliation":[{"name":"National University of Pharmacy , , Hryhoriia Skovorody Str, 53 , ,","place":["Kharkiv, Ukraine, 61002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1139-6296","authenticated-orcid":true,"given":"Liubov","family":"Galuzinska","sequence":"additional","affiliation":[{"name":"National University of Pharmacy , , Hryhoriia Skovorody Str, 53 , ,","place":["Kharkiv, Ukraine, 61002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmytro","family":"Lytkin","sequence":"additional","affiliation":[{"name":"National University of Pharmacy , , Hryhoriia Skovorody Str, 53 , ,","place":["Kharkiv, Ukraine, 61002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2191-8617","authenticated-orcid":true,"given":"Julija","family":"Razumiene","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Life Sciences Center Vilnius University , , Sauletekio Av. 7 , ,","place":["Vilnius, Lithuania, LT- 10257"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"2026081109101271400_cit1","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1159\/000368940","article-title":"Update on Inflammation in Chronic Kidney Disease","volume":"39","author":"Akchurin","year":"2015","journal-title":"Blood Purif"},{"key":"2026081109101271400_cit2","doi-asserted-by":"publisher","first-page":"e225","DOI":"10.1210\/clinem\/dgaf281","article-title":"Urine Choline Oxidation Metabolites Predict Chronic Kidney Disease\nProgression in Patients With Type 2 Diabetes","volume":"111","author":"Liu","year":"2025","journal-title":"J. Clin Endocrinol. Metab."},{"key":"2026081109101271400_cit3","doi-asserted-by":"publisher","first-page":"3188","DOI":"10.2169\/internalmedicine.4895-24","article-title":"Significance of Serum Cholinesterase as a Prognostic\nMarker in Patients with Non-dialysis-dependent Chronic Kidney Disease","volume":"64","author":"Okamoto","year":"2025","journal-title":"IIntern. Med."},{"key":"2026081109101271400_cit4","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1111\/j.1365-2796.2009.02098.x","article-title":"Cholinergic control of inflammation","volume":"265","author":"Rosas-Ballina","year":"2009","journal-title":"J. Intern Med."},{"key":"2026081109101271400_cit5","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-37935-3","article-title":"Neurological sequel\nof chronic kidney disease: From diminished Acetylcholinesterase activity\nto mitochondrial dysfunctions, oxidative stress and inflammation in\nmice brain","volume":"9","author":"Mazumder","year":"2019","journal-title":"Sci. Rep."},{"key":"2026081109101271400_cit6","doi-asserted-by":"publisher","DOI":"10.3390\/toxins13020142","article-title":"Uremic\nToxins in the Progression of Chronic Kidney Disease and Cardiovascular\nDisease: Mechanisms and Therapeutic Targets","volume":"13","author":"Lim","year":"2021","journal-title":"Toxins"},{"key":"2026081109101271400_cit7","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.fct.2015.02.009","article-title":"Theanine prevents doxorubicin-induced acute hepatotoxicity\nby reducing intrinsic apoptotic response","volume":"78","author":"Nagai","year":"2015","journal-title":"Food\nChem. Toxicol."},{"key":"2026081109101271400_cit8","doi-asserted-by":"publisher","DOI":"10.4103\/2141-9248.126619","article-title":"An evaluation of hepatotoxicity in breast cancer patients receiving\ninjection doxorubicin","volume":"4","author":"Damodar","year":"2014","journal-title":"Ann. Med. Health Sci.\nRes."},{"key":"2026081109101271400_cit9","doi-asserted-by":"publisher","first-page":"31","DOI":"10.4103\/2229-516X.149232","article-title":"A comparative\nstudy of serum aminotransferases in chronic kidney disease with and\nwithout end-stage renal disease: Need for new reference ranges","volume":"5","author":"Ray","year":"2015","journal-title":"Int. J. Appl. Basic Med. Res."},{"key":"2026081109101271400_cit10","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.1093\/ndt\/gfaf029","article-title":"Cholinergic system in patients with chronic\nkidney disease: cognitive and renal implications","volume":"40","author":"Xu","year":"2025","journal-title":"Nephrol., Dial., Transplant."},{"key":"2026081109101271400_cit11","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.782745","article-title":"Metabolic Effects of Doxorubicin\non the Rat Liver Assessed With Hyperpolarized MRI and Metabolomics","volume":"12","author":"Timm","year":"2022","journal-title":"Front. Physiol."},{"key":"2026081109101271400_cit12","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s002280000259","article-title":"The effect\nof community-acquired pneumonia on plasma\nesterases in older people","volume":"57","author":"Abou-Hatab","year":"2001","journal-title":"Eur. J. Clin Pharmacol"},{"key":"2026081109101271400_cit13","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1007\/s00228-008-0499-1","article-title":"Plasma\nesterases and inflammation in ageing and frailty","volume":"64","author":"Hubbard","year":"2008","journal-title":"Eur. J. Clin Pharmacol"},{"key":"2026081109101271400_cit14","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.talanta.2010.04.061","article-title":"A sensitive\ncholine biosensor with supramolecular architecture","volume":"82","author":"Zhang","year":"2010","journal-title":"Talanta"},{"key":"2026081109101271400_cit15","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2023.115724","article-title":"Acetylcholinesterase\nbiosensors for electrochemical\ndetection of neurotoxic pesticides and acetylcholine neurotransmitter:\nA literature review","volume":"227","author":"Rajagopalan","year":"2023","journal-title":"Environ. Res."},{"key":"2026081109101271400_cit16","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.trac.2018.11.035","article-title":"Enzyme-based biosensors\nfor choline analysis: A review","volume":"110","author":"Rahimi","year":"2019","journal-title":"TrAC, Trends\nAnal. Chem."},{"key":"2026081109101271400_cit17","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1039\/C7AN01757J","article-title":"Assay of serum cholinesterase activity\nby an amperometric biosensor based on a co-crosslinked choline oxidase\/overoxidized\npolypyrrole bilayer","volume":"143","author":"Ciriello","year":"2018","journal-title":"Analyst"},{"key":"2026081109101271400_cit18","doi-asserted-by":"publisher","first-page":"1828","DOI":"10.1021\/es202689u","article-title":"Highly Sensitive\nand Selective Immuno-Capture\/Electrochemical\nAssay of Acetylcholinesterase Activity in Red Blood Cells: A Biomarker\nof Exposure to Organophosphorus Pesticides and Nerve Agents","volume":"46","author":"Chen","year":"2012","journal-title":"Environ. Sci. Technol."},{"key":"2026081109101271400_cit19","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.snb.2011.07.001","article-title":"Screen-printed carbon electrode for choline based on\nMnO2 nanoparticles and choline oxidase\/polyelectrolyte layers","volume":"159","author":"Dontsova","year":"2011","journal-title":"Sens. Actuators, B"},{"key":"2026081109101271400_cit20","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1021\/ac034757v","article-title":"Acetylcholine\nand Choline Amperometric Enzyme Sensors Characterized in Vitro and\nin Vivo","volume":"76","author":"Mitchell","year":"2004","journal-title":"Anal. Chem."},{"key":"2026081109101271400_cit21","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbsr.2025.100927","article-title":"Electrochemical\ndetection of choline via oxygen consumption\nin a thermally reduced graphene oxide matrix: Advantages of operation\nat both positive and negative potentials","volume":"50","author":"Sakinyte-Urbikiene","year":"2025","journal-title":"Sens.\nBiosens. Res."},{"key":"2026081109101271400_cit22","unstructured":"Imamura, A.\n          \n          O-Acetylation\nusing acetic anhydride in pyridine. 2023."},{"key":"2026081109101271400_cit23","doi-asserted-by":"publisher","first-page":"21","DOI":"10.4103\/2229-5186.79345","article-title":"Methods for the determination\nof limit of detection and limit of\nquantitation of the analytical methods","volume":"2","author":"Shrivastava","year":"2011","journal-title":"Chron.\nYoung Sci."},{"key":"2026081109101271400_cit24","doi-asserted-by":"publisher","first-page":"1516","DOI":"10.1007\/s10910-007-9237-7","article-title":"Apparent Michaelis constant of the enzyme modified\nporous electrode","volume":"43","author":"Ivanauskas","year":"2008","journal-title":"J. Math. Chem."},{"key":"2026081109101271400_cit25","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1002\/ame2.12194","article-title":"Folic acid-induced\nanimal model of kidney disease","volume":"4","author":"Yan","year":"2021","journal-title":"Animal Models\nExp. Med."},{"key":"2026081109101271400_cit26","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1159\/000521220","article-title":"Dexrazoxane\nAlleviated Doxorubicin-Induced Nephropathy in Rats","volume":"107","author":"Hu","year":"2022","journal-title":"Pharmacology"},{"key":"2026081109101271400_cit27","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1093\/oxfordjournals.jbchem.a132949","article-title":"Identification and\nproperties of the prosthetic group of choline oxidase from Alcaligenes\nsp","volume":"88","author":"Ohta-Fukuyama","year":"1980","journal-title":"J. Biochem."},{"key":"2026081109101271400_cit28","doi-asserted-by":"publisher","first-page":"127","DOI":"10.2116\/analsci.11.127","article-title":"Rapid Measurement of\nCholinesterase Activity Using\nan Amperometric Enzyme Electrode Based on Lipid-Modified Choline Oxidase","volume":"11","author":"Mizutani","year":"1995","journal-title":"Anal. Sci."},{"key":"2026081109101271400_cit29","doi-asserted-by":"publisher","first-page":"13821","DOI":"10.1021\/ja204116a","article-title":"The \u201cNeutral\u201d Hydrolysis of Simple Carboxylic Esters\nin Water and the Rate Enhancements Produced by Acetylcholinesterase\nand Other Carboxylic Acid Esterases","volume":"133","author":"Wolfenden","year":"2011","journal-title":"J. Am.\nChem. Soc."},{"key":"2026081109101271400_cit30","doi-asserted-by":"publisher","first-page":"2462","DOI":"10.1021\/ja020850+","article-title":"Fundamental\nreaction mechanism for\ncocaine hydrolysis in human butyrylcholinesterase","volume":"125","author":"Zhan","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"2026081109101271400_cit31","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/0009-8981(91)90302-S","article-title":"Rapid and\nsensitive discriminating determination of acetylcholinesterase activity\nin amniotic fluid with a choline sensor","volume":"203","author":"Morelis","year":"1991","journal-title":"Clin.\nChim. Acta"},{"key":"2026081109101271400_cit32","doi-asserted-by":"publisher","first-page":"32464","DOI":"10.1039\/D5RA04585A","article-title":"Measurement of acetylcholinesterase activity\nby electrochemical analysis method utilizing organocatalytic reactions","volume":"15","author":"Ono","year":"2025","journal-title":"RSC Adv."},{"key":"2026081109101271400_cit33","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.15942","article-title":"Caloric restriction\nreduces proteinuria in male rats with established nephropathy","volume":"12","author":"Sijbesma","year":"2024","journal-title":"Phys. Rep."},{"key":"2026081109101271400_cit34","doi-asserted-by":"publisher","DOI":"10.3390\/biom16010042","article-title":"Association of Oxidative\nStress Markers\nwith Cardio-Kidney-Metabolic Parameters and Cardiovascular Disease\nin Patients with Type 2 Diabetes Mellitus","volume":"16","author":"Roumeliotis","year":"2026","journal-title":"Biomolecules"},{"key":"2026081109101271400_cit35","doi-asserted-by":"publisher","DOI":"10.3390\/ijms262110670","article-title":"Assessment\nof AOPP, TBARS, and Inflammatory Status\nin Diabetic Nephropathy and Hemodialyzed Patients","volume":"26","author":"Caragea","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"2026081109101271400_cit36","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.nefroe.2025.02.009","article-title":"Oxidative\nstress and\ninflammation on metabolic abnormalities and renal involvement in prediabetic\nsubjects across Europe","volume":"45","author":"Mas-Fontao","year":"2025","journal-title":"Nefrologi\u0301a"},{"key":"2026081109101271400_cit37","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13060751","article-title":"Potentials\nof Natural Antioxidants in Reducing\nInflammation and Oxidative Stress in Chronic Kidney Disease","volume":"13","author":"Lee","year":"2024","journal-title":"Antioxidants"},{"key":"2026081109101271400_cit38","doi-asserted-by":"publisher","DOI":"10.3892\/wasj.2024.281","article-title":"Biochemical variations in patients\nwith renal failure: A comparative study","volume":"6","author":"Abo-Ghneim","year":"2024","journal-title":"World\nAcad. Sci. J."},{"key":"2026081109101271400_cit39","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/liv.13305","article-title":"Why and how to measure\nrenal function in patients with liver disease","volume":"37","author":"Piano","year":"2017","journal-title":"Liver Int."},{"key":"2026081109101271400_cit40","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s001340050780","article-title":"Renal failure\nin liver disease","volume":"25","author":"Eckardt","year":"1999","journal-title":"Intensive Care Med."},{"key":"2026081109101271400_cit41","doi-asserted-by":"publisher","first-page":"98","DOI":"10.22074\/cellj.2023.2007757.1376","article-title":"Review\non Kidney-Liver\nCrosstalk: Pathophysiology of Their Disorders","volume":"26","author":"Rad","year":"2024","journal-title":"Cell J."}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c01440","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/31\/22771\/65884677\/acs.analchem.6c01440.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/31\/22771\/65884677\/acs.analchem.6c01440.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T13:10:18Z","timestamp":1786453818000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/31\/22771\/5207029\/Electrochemical-Biosensor-Based-Evaluation-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,12]]},"references-count":41,"journal-issue":{"issue":"31","published-online":{"date-parts":[[2026,7,12]]},"published-print":{"date-parts":[[2026,8,11]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c01440","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,12]]}}}