{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:00:08Z","timestamp":1787655608063,"version":"build-2736575974"},"reference-count":66,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T00:00:00Z","timestamp":1665100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The phenolic drug molecules can be metabolized, among others, by the small intestine\u2019s enterocytes. The conjugation reactions (glucuronidation and sulfation) show great importance in these transformations, although the oxidation reactions can be significant. These processes are dependent on the substituents of the phenolic compounds or the reacting functional groups (hydroxyl or carboxyl). Pathologic conditions, e.g., permanent hyperglycemia and diabetes, can alter the activities of the conjugative and possibly the oxidative enzymes, thus forming a change in the metabolic pattern and eventually provoking oxidative stress. A rat intestinal perfusion model was used to investigate the way in which experimental hyperglycemia affects the paracetamol\u2019s intestinal elimination and metabolism. Hyperglycemia was induced by the administration of streptozotocin. Two hundred and fifty \u00b5M paracetamol was used in the intestinal perfusion solution. For the quantitation of the paracetamol and its major metabolites in the intestinal perfusate, an isocratic high-performance liquid chromatography method with UV-Vis detection was developed. The results revealed that quantities of all of the measured metabolites (glucuronide, sulfate, cysteine, and mercapturic acid conjugates) increased as the effect of the streptozotocin-induced hyperglycemia also did. In the small intestine\u2019s homogenate, the glutathione levels showed that there was a decrease in the hyperglycemia levels after the paracetamol administration. In contrast, the tissue levels of the cysteine were lower in the streptozotocin-induced hyperglycemia and increased after the administration of the paracetamol. The changes in the activity of the intestinal CYP 3A4, CYP 2E1, and cyclooxygenase (COX) enzymes were determined in the control and the hyperglycemic cases. Still, there was a significant observable enzyme activity elevation in the intestinal COX enzymes, but there was a decrease in the amount of activity of the intestinal CYP3A4 enzymes, and the CYP2E1 enzyme activity was practically changeless. The results on the cysteine levels in the intestinal homogenate, at least partly, can be explained by the regulation function of the cysteine during the occurrence of oxidative stress.<\/jats:p>","DOI":"10.3390\/ijms231911913","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"11913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Investigation of Intestinal Absorption and Excretion of Paracetamol in Streptozotocin-Induced Hyperglycemia"],"prefix":"10.3390","volume":"23","author":[{"given":"Petra","family":"M\u00e9sz\u00e1ros","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of P\u00e9cs, R\u00f3kus utca 4, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e1ra","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of P\u00e9cs, R\u00f3kus utca 4, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4098-1072","authenticated-orcid":false,"given":"Gy\u0151z\u0151","family":"Kulcs\u00e1r","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of P\u00e9cs, R\u00f3kus utca 4, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"P\u00e1skuj","sequence":"additional","affiliation":[{"name":"Sandoz Novartis Division, 018953 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Alm\u00e1si","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of P\u00e9cs, R\u00f3kus utca 4, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jbbm.2006.05.002","article-title":"A simple and rapid ion-pair HPLC method for simultaneous quantitation of 4-nitrophenol and its glucuronide and sulfate conjugates","volume":"69","author":"Fischer","year":"2006","journal-title":"J. Biochem. Biophys. Methods"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1021\/tx9701687","article-title":"Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6","volume":"11","author":"Chen","year":"1998","journal-title":"Chem. Res Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1139\/cjpp-2015-0065","article-title":"Effect of experimental diabetes and insulin replacement on intestinal metabolism and excretion of 4-nitrophenol in rats","volume":"93","author":"Fischer","year":"2015","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1139\/cjpp-2019-0164","article-title":"Investigation of intestinal elimination and biliary excretion of ibuprofen in hyperglycemic rats","volume":"97","author":"Garai","year":"2019","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mohammed, H.O., Alm\u00e1si, A., Moln\u00e1r, S., and Perj\u00e9si, P. (2022). The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia. Molecules, 27.","DOI":"10.3390\/molecules27134000"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/bcpt.13137","article-title":"Expression of clinically relevant drug-metabolizing enzymes along the human intestine and their correlation to drug transporters and nuclear receptors: An intra-subject analysis","volume":"124","author":"Fritz","year":"2019","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1124\/dmd.31.12.1520","article-title":"The small intestine as a xenobiotic-metabolizing organ","volume":"31","author":"Kaminsky","year":"2003","journal-title":"Drug Metab. Dispos."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.joen.2015.01.024","article-title":"Acetaminophen: Old Drug, New Issues","volume":"41","author":"Aminoshariae","year":"2015","journal-title":"J. Endod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/j.1527-3458.2006.00250.x","article-title":"Paracetamol: New Vistas of an Old Drug","volume":"12","author":"Bertolini","year":"2006","journal-title":"CNS Drug Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1080\/23328940.2021.1886392","article-title":"Paracetamol (acetaminophen): A familiar drug with an unexplained mechanism of action","volume":"8","author":"Ayoub","year":"2021","journal-title":"Temperature"},{"key":"ref_11","first-page":"3","article-title":"Paracetamol\u2014An old drug with new mechanisms of action","volume":"48","author":"Szychowski","year":"2020","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1093\/bjaceaccp\/mkt049","article-title":"Paracetamol: Mechanisms and updates","volume":"14","author":"Sharma","year":"2014","journal-title":"Contin. Educ. Anaesth. Crit. Care Pain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/j.1365-2710.2009.01143.x","article-title":"What do we (not) know about how paracetamol (acetaminophen) works?","volume":"35","author":"Toussaint","year":"2010","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"291S","DOI":"10.1111\/j.1365-2125.1980.tb01812.x","article-title":"Kinetics and metabolism of paracetamol and phenacetin","volume":"10","author":"Prescott","year":"1980","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/papr.12130","article-title":"Acetaminophen (Paracetamol) Oral Absorption and Clinical Influences","volume":"14","author":"Raffa","year":"2014","journal-title":"Pain Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2165\/00003088-198207020-00001","article-title":"Clinical Pharmacokinetics of Paracetamol","volume":"7","author":"Forrest","year":"1982","journal-title":"Clin. Pharmacokinet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1097\/FPC.0000000000000150","article-title":"PharmGKB summary: Pathways of acetaminophen metabolism at the therapeutic versus toxic doses","volume":"25","author":"Mazaleuskaya","year":"2015","journal-title":"Pharmacogenet. Genom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1007\/s11095-013-1007-6","article-title":"Metabolism and Disposition of Acetaminophen: Recent Advances in Relation to Hepatotoxicity and Diagnosis","volume":"30","author":"McGill","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2165\/00002018-200528030-00004","article-title":"Tolerability of Paracetamol","volume":"28","author":"Graham","year":"2005","journal-title":"Drug Saf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1097\/00045391-200205000-00008","article-title":"Analgesics and Glutathione","volume":"9","author":"Lauterburg","year":"2002","journal-title":"Am. J. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s10787-013-0172-x","article-title":"The modern pharmacology of paracetamol: Therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings","volume":"21","author":"Graham","year":"2013","journal-title":"Inflammopharmacology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/febs.15842","article-title":"Understanding the role of cysteine in ferroptosis: Progress & paradoxes","volume":"289","author":"Poltorack","year":"2022","journal-title":"FEBS J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.jsps.2015.03.013","article-title":"Diabetes mellitus and oxidative stress\u2014A concise review","volume":"24","author":"Asmat","year":"2016","journal-title":"Saudi Pharm. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1089\/ars.2005.7.1476","article-title":"Hyperglycemia-induced reactive oxygen species and impaired endothelial progenitor cell function","volume":"7","author":"Callaghan","year":"2005","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1177\/0394632015572564","article-title":"The possible role of glutathione-S-transferase activity in diabetic nephropathy","volume":"28","author":"Tesauro","year":"2015","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Correia, M.J., Pimp\u00e3o, A.B., Fernandes, D.G.F., Morello, J., Sequeira, C.O., Calado, J., Antunes, A.M.M., Almeida, M.S., Branco, P., and Monteiro, E.C. (2022). Cysteine as a Multifaceted Player in Kidney, the Cysteine-Related Thiolome and Its Implications for Precision Medicine. Molecules, 27.","DOI":"10.3390\/molecules27041416"},{"key":"ref_27","first-page":"5.47.1","article-title":"Streptozotocin-Induced Diabetic Models in Mice and Rats","volume":"70","author":"Furman","year":"2015","journal-title":"Curr. Protoc. Pharmac."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"537","DOI":"10.33549\/physiolres.930111","article-title":"The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas","volume":"50","author":"Szkudelski","year":"2001","journal-title":"Physiol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0378-4347(99)00290-X","article-title":"Simple and rapid assay for acetaminophen and conjugated metabolites in low-volume serum samples","volume":"732","author":"Brunner","year":"1999","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S0731-7085(03)00573-9","article-title":"The quantification of paracetamol, paracetamol glucuronide and paracetamol sulphate in plasma and urine using a single high-performance liquid chromatography assay","volume":"34","author":"Jensen","year":"2004","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0731-7085(03)00246-2","article-title":"Development and optimization of a reversed-phase high-performance liquid chromatographic method for the determination of acetaminophen and its major metabolites in rabbit plasma and urine after a toxic dose","volume":"32","author":"Vertzoni","year":"2003","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_32","first-page":"2051","article-title":"Simultaneous determination of paracetamol and its metabolites in rat serum by HPLC method and its application supplement-drug pharmacokinetic interaction","volume":"39","author":"Alkhawaja","year":"2014","journal-title":"Int. J. Pharm. Anal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/0731-7085(94)00859-0","article-title":"The estimation of paracetamol and its major metabolites in both plasma and urine by a single high-performance liquid chromatography assay","volume":"12","author":"Lau","year":"1994","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0378-4347(92)80483-7","article-title":"Determination of paracetamol and its four major metabolites in mouse plasma by reversed-phase ion-pair high-performance liquid chromatography","volume":"573","author":"Esteban","year":"1992","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1126\/science.aar3318","article-title":"Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection","volume":"359","author":"Thaiss","year":"2018","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1159\/000354449","article-title":"Acetaminophen changes intestinal epithelial cell membrane properties, subsequently affecting absorption processes","volume":"32","author":"Tollabimazraehno","year":"2013","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1111\/j.1365-2125.2012.04402.x","article-title":"Pharmacokinetics of paracetamol and its metabolites in women at delivery and post-partum","volume":"75","author":"Kulo","year":"2013","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3109\/00498258309052218","article-title":"Biliary excretion and enterohepatic circulation of paracetamol in the rat","volume":"13","author":"Siegers","year":"1983","journal-title":"Xenobiotica"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1042\/cs0580379","article-title":"Renal metabolism of paracetamol: Studies in the isolated perfused rat kidney","volume":"58","author":"Hart","year":"1980","journal-title":"Clin. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1556\/APhysiol.99.2012.002","article-title":"Metabolic enzyme activities and drug excretion in the small intestine and in the liver in the rat","volume":"100","author":"Bojcsev","year":"2013","journal-title":"Acta Physiol. Hung."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1111\/j.1476-5381.2011.01270.x","article-title":"Significantly reduced cytochrome P450 3A4 expression and activity in liver from humans with diabetes mellitus","volume":"163","author":"Dostalek","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1080\/01480545.2019.1566354","article-title":"Susceptibility to the acute toxicity of acrylonitrile in streptozotocin-induced diabetic rats: Protective effect of phenethyl isothiocyanate, a phytochemical CYP2E1 inhibitor","volume":"44","author":"Li","year":"2021","journal-title":"Drug Chem. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1210\/jcem-71-4-1036","article-title":"Cytochrome P450IIE1 is elevated in lymphocytes from poorly controlled insulin-dependent diabetics","volume":"71","author":"Song","year":"1990","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/j.1472-8206.1998.tb00985.x","article-title":"Cytochrome P450 2E1 activity in diabetic and obese patients as assessed by chlorzoxazone hydroxylation","volume":"12","author":"Lucas","year":"1998","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1211\/jpp.62.07.0009","article-title":"Effects of insulin on CYP3A activity and nicardipine disposition in streptozotocin-induced diabetic rats","volume":"62","author":"Hasegawa","year":"2010","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.2337\/db07-0740","article-title":"Protective effects of cyclooxygenase-2 gene inactivation against peripheral nerve dysfunction and intraepidermal nerve fiber loss in experimental diabetes","volume":"56","author":"Kellogg","year":"2007","journal-title":"Diabetes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1067\/mcp.2000.104736","article-title":"Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation","volume":"67","author":"Manyike","year":"2000","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_48","first-page":"18370","article-title":"Intestinal cytochromes P450 regulating the intestinal microbiota and its probiotic profile","volume":"23","author":"Bezirtzoglou","year":"2012","journal-title":"Microb. Ecol. Health Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/BF03190865","article-title":"Expression of genes encoding for drug metabolising cytochrome P450 enzymes and P-glycoprotein in the rat small intestine; comparison to the liver","volume":"28","author":"Lindell","year":"2003","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1211\/jpp.61.05.0002","article-title":"Cytochrome P450-mediated metabolism in the human gut wall","volume":"61","author":"Thelen","year":"2009","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.freeradbiomed.2007.12.005","article-title":"Acute hyperglycemia and oxidative stress: Direct cause and effect?","volume":"44","author":"Choi","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"18373","DOI":"10.1039\/D2RA02469A","article-title":"A review on the degradation of acetaminophen by advanced oxidation process: Pathway, by-products, biotoxicity, and density functional theory calculation","volume":"12","author":"Qutob","year":"2022","journal-title":"RSC Adv."},{"key":"ref_53","unstructured":"Mohammed, H.O., Alm\u00e1si, A., Kun, B., Wittmann, I., and Perj\u00e9si, P. (2022). Study on oxidative transformations of endogenous lipids, proteins, and amino acids in hyperglycaemic rats, Sent\u00a0for\u00a0publication."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4946","DOI":"10.1111\/j.1742-4658.2009.07197.x","article-title":"Oxidative stress induces a reversible flux of cysteine from tissues to blood in vivo in the rat","volume":"276","author":"Giustarini","year":"2009","journal-title":"FEBS J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"30033","DOI":"10.1038\/srep30033","article-title":"Crosstalk between cystine and glutathione is critical for the regulation of amino acid signaling pathways and ferroptosis","volume":"6","author":"Yu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00726-011-0867-5","article-title":"The oxidative stress-inducible cystine\/glutamate antiporter, system x (c) (-): Cystine supplier and beyond","volume":"42","author":"Conrad","year":"2012","journal-title":"Amino Acids"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3109\/00498254.2016.1166533","article-title":"The acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) inhibits glutathione synthetase in vitro; a clue to the mechanism of 5-oxoprolinuric acidosis?","volume":"47","author":"Walker","year":"2017","journal-title":"Xenobiotica"},{"key":"ref_58","first-page":"525","article-title":"Enterohepatic circulation of the mercapturic acid and cysteine conjugates of propachlor","volume":"9","author":"Bakke","year":"1981","journal-title":"Drug Metab. Dispos."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/0006-2952(79)90402-7","article-title":"Paracetamol metabolism in the isolated perfused rat liver with further metabolism of a biliary paracetamol conjugate by the small intestine","volume":"28","author":"Ormstad","year":"1979","journal-title":"Biochem. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/20014091111677","article-title":"Paracetamol (acetaminophen)-induced toxicity: Molecular and biochemical mechanisms, analogues and protective approaches","volume":"31","author":"Bessems","year":"2001","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/S0006-2952(97)00659-X","article-title":"Cellular distribution of N-acetyltransferase activity in the rat small intestine","volume":"55","author":"Ware","year":"1998","journal-title":"Biochem. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Heard, K.J., Green, J.L., James, L.P., Judge, B.S., Zolot, L., Rhyee, S., and Dart, R.C. (2011). Acetaminophen-cysteine adducts during therapeutic dosing and following overdose. BMC Gastroenterol., 11.","DOI":"10.1186\/1471-230X-11-20"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1746985","DOI":"10.1155\/2016\/1746985","article-title":"Validation of a Reversed-Phase High Performance Liquid Chromatography Method for the Simultaneous Analysis of Cysteine and Reduced Glutathione in Mouse Organs","volume":"2016","author":"Brundu","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_64","first-page":"19","article-title":"Screening of some selected plants for CYP3A inhibition and bioavailability enhancement","volume":"1","author":"Zaveri","year":"2011","journal-title":"Adv. Res. Pharm. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jchromb.2006.02.006","article-title":"Validation of a HPLC method for the determination of p-nitrophenol hydroxylase activity in rat hepatic microsomes","volume":"834","author":"Elbarbry","year":"2006","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1093\/carcin\/13.4.533","article-title":"Bioactivation of aflatoxin B1 by lipoxygenases, prostaglandin H synthase and cytochrome P450 monooxygenase in guinea-pig tissues","volume":"13","author":"Liu","year":"1992","journal-title":"Carcinogenesis"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11913\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:47:49Z","timestamp":1760143669000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11913"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,7]]},"references-count":66,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911913"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911913","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,7]]}}}