{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T19:22:39Z","timestamp":1777490559025,"version":"3.51.4"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T00:00:00Z","timestamp":1660348800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T00:00:00Z","timestamp":1660348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Leibniz-Institut f\u00fcr Arbeitsforschung (IfADo)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypoalbuminemia (HA) is frequently observed in systemic inflammatory diseases and in liver disease. However, the influence of HA on the pharmacokinetics and toxicity of compounds with high plasma albumin binding remained insufficiently studied. The \u2018<jats:italic>lack-of-delivery-concept<\/jats:italic>\u2019 postulates that HA leads to less carrier mediated uptake of albumin bound substances into hepatocytes and to less glomerular filtration; in contrast, the \u2018<jats:italic>concept-of-higher-free-fraction<\/jats:italic>\u2019 argues that increased concentrations of non-albumin bound compounds facilitate hepatocellular uptake and enhance glomerular filtration. To address this question, we performed intravital imaging on livers and kidneys of anesthetized mice to quantify the spatio-temporal tissue distribution of the mycotoxin ochratoxin A (OTA) based on its auto-fluorescence in albumin knockout and wild-type mice. HA strongly enhanced the uptake of OTA from the sinusoidal blood into hepatocytes, followed by faster secretion into bile canaliculi. These toxicokinetic changes were associated with increased hepatotoxicity in heterozygous albumin knockout mice for which serum albumin was reduced to a similar extent as in patients with severe hypoalbuminemia. HA also led to a shorter half-life of OTA in renal capillaries, increased glomerular filtration, and to enhanced uptake of OTA into tubular epithelial cells. In conclusion, the results favor the \u2018<jats:italic>concept-of-higher-free-fraction<\/jats:italic>\u2019 in HA; accordingly, HA causes an increased tissue uptake of compounds with high albumin binding and increased organ toxicity. It should be studied if this concept can be generalized to all compounds with high plasma albumin binding that are substrates of hepatocyte and renal tubular epithelial cell carriers.<\/jats:p>","DOI":"10.1007\/s00204-022-03361-8","type":"journal-article","created":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T12:06:34Z","timestamp":1660392394000},"page":"2967-2981","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Hypoalbuminemia affects the spatio-temporal tissue distribution of ochratoxin A in liver and kidneys: consequences for organ toxicity"],"prefix":"10.1007","volume":"96","author":[{"given":"Reham","family":"Hassan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Friebel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Brackhagen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaynab","family":"Hobloss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maiju","family":"Myllys","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiebke","family":"Albrecht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elsayed S. I.","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdel-latif","family":"Seddek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemarie","family":"Marchan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Cadenas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedikt","family":"Cramer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Ulrich","family":"Humpf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Hartl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedikt","family":"Simbrunner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Reiberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Hoehme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisela H.","family":"Degen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan G.","family":"Hengstler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0695-3403","authenticated-orcid":false,"given":"Ahmed","family":"Ghallab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,8,13]]},"reference":[{"issue":"6","key":"3361_CR1","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.3390\/toxins2061381","volume":"2","author":"N Anzai","year":"2010","unstructured":"Anzai N, Jutabha P, Endou H (2010) Molecular mechanism of ochratoxin a transport in the kidney. Toxins (basel) 2(6):1381\u20131398. https:\/\/doi.org\/10.3390\/toxins2061381","journal-title":"Toxins (basel)"},{"issue":"4","key":"3361_CR2","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1002\/ueg2.12089","volume":"9","author":"L Balcar","year":"2021","unstructured":"Balcar L, Semmler G, Pomej K et al (2021) Patterns of acute decompensation in hospitalized patients with cirrhosis and course of acute-on-chronic liver failure. United Eur Gastroenterol J 9(4):427\u2013437. https:\/\/doi.org\/10.1002\/ueg2.12089","journal-title":"United Eur Gastroenterol J"},{"issue":"4","key":"3361_CR3","first-page":"733","volume":"75","author":"AM Bendele","year":"1985","unstructured":"Bendele AM, Carlton WW, Krogh P, Lillehoj EB (1985) Ochratoxin A carcinogenesis in the (C57BL\/6J X C3H)F1 mouse. J Natl Cancer Inst 75(4):733\u2013742","journal-title":"J Natl Cancer Inst"},{"issue":"12","key":"3361_CR4","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1038\/s41592-019-0582-9","volume":"16","author":"S Berg","year":"2019","unstructured":"Berg S, Kutra D, Kroeger T et al (2019) Ilastik: interactive machine learning for (bio)image analysis. Nat Methods 16(12):1226\u20131232. https:\/\/doi.org\/10.1038\/s41592-019-0582-9","journal-title":"Nat Methods"},{"issue":"1","key":"3361_CR5","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s00204-019-02630-3","volume":"94","author":"G Campos","year":"2020","unstructured":"Campos G, Schmidt-Heck W, De Smedt J et al (2020) Inflammation-associated suppression of metabolic gene networks in acute and chronic liver disease. Arch Toxicol 94(1):205\u2013217. https:\/\/doi.org\/10.1007\/s00204-019-02630-3","journal-title":"Arch Toxicol"},{"issue":"4","key":"3361_CR6","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.jhep.2020.10.004","volume":"74","author":"D Costa","year":"2021","unstructured":"Costa D, Simbrunner B, Jachs M et al (2021) Systemic inflammation increases across distinct stages of advanced chronic liver disease and correlates with decompensation and mortality. J Hepatol 74(4):819\u2013828. https:\/\/doi.org\/10.1016\/j.jhep.2020.10.004","journal-title":"J Hepatol"},{"issue":"3","key":"3361_CR7","doi-asserted-by":"publisher","first-page":"187","DOI":"10.3109\/10408444.2010.529103","volume":"41","author":"SC Duarte","year":"2011","unstructured":"Duarte SC, Pena A, Lino CM (2011) Human ochratoxin a biomarkers\u2013from exposure to effect. Crit Rev Toxicol 41(3):187\u2013212. https:\/\/doi.org\/10.3109\/10408444.2010.529103","journal-title":"Crit Rev Toxicol"},{"issue":"5","key":"3361_CR8","first-page":"6113","volume":"18","author":"EFSA","year":"2020","unstructured":"EFSA (2020) Scientific opinion on the risks to public health related to the presence of ochratoxin A in food. EFSA J 18(5):6113","journal-title":"EFSA J"},{"issue":"3","key":"3361_CR9","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.mam.2011.12.002","volume":"33","author":"G Fanali","year":"2012","unstructured":"Fanali G, di Masi A, Trezza V, Marino M, Fasano M, Ascenzi P (2012) Human serum albumin: from bench to bedside. Mol Aspects Med 33(3):209\u2013290. https:\/\/doi.org\/10.1016\/j.mam.2011.12.002","journal-title":"Mol Aspects Med"},{"key":"3361_CR10","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.addr.2017.01.005","volume":"116","author":"B George","year":"2017","unstructured":"George B, You D, Joy MS, Aleksunes LM (2017) Xenobiotic transporters and kidney injury. Adv Drug Deliv Rev 116:73\u201391. https:\/\/doi.org\/10.1016\/j.addr.2017.01.005","journal-title":"Adv Drug Deliv Rev"},{"issue":"2","key":"3361_CR11","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1002\/hep.30213","volume":"69","author":"A Ghallab","year":"2019","unstructured":"Ghallab A, Hofmann U, Sezgin S et al (2019a) Bile microinfarcts in cholestasis are initiated by rupture of the apical hepatocyte membrane and cause shunting of bile to sinusoidal blood. Hepatology 69(2):666\u2013683. https:\/\/doi.org\/10.1002\/hep.30213","journal-title":"Hepatology"},{"key":"3361_CR12","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121556","author":"A Ghallab","year":"2019","unstructured":"Ghallab A, Myllys M, Holland CH et al (2019b) Influence of liver fibrosis on lobular zonation. Cells. https:\/\/doi.org\/10.3390\/cells8121556","journal-title":"Cells"},{"issue":"6","key":"3361_CR13","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1007\/s00204-021-03073-5","volume":"95","author":"A Ghallab","year":"2021","unstructured":"Ghallab A, Hassan R, Myllys M et al (2021a) Subcellular spatio-temporal intravital kinetics of aflatoxin B1 and ochratoxin A in liver and kidney. Arch Toxicol 95(6):2163\u20132177. https:\/\/doi.org\/10.1007\/s00204-021-03073-5","journal-title":"Arch Toxicol"},{"issue":"10","key":"3361_CR14","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.3390\/cells10102516","volume":"10","author":"A Ghallab","year":"2021","unstructured":"Ghallab A, Myllys M, Friebel A et al (2021b) Spatio-temporal multiscale analysis of western diet-fed mice reveals a translationally relevant sequence of events during NAFLD progression. Cells 10(10):2516","journal-title":"Cells"},{"issue":"1","key":"3361_CR15","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.jhep.2022.01.020","volume":"77","author":"A Ghallab","year":"2022","unstructured":"Ghallab A, Hassan R, Hofmann U et al (2022) Interruption of bile acid uptake by hepatocytes after acetaminophen overdose ameliorates hepatotoxicity. J Hepatol 77(1):71\u201383. https:\/\/doi.org\/10.1016\/j.jhep.2022.01.020","journal-title":"J Hepatol"},{"issue":"8","key":"3361_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109526","volume":"36","author":"K Gianmoena","year":"2021","unstructured":"Gianmoena K, Gasparoni N, Jashari A et al (2021) Epigenomic and transcriptional profiling identifies impaired glyoxylate detoxification in NAFLD as a risk factor for hyperoxaluria. Cell Rep 36(8):109526. https:\/\/doi.org\/10.1016\/j.celrep.2021.109526","journal-title":"Cell Rep"},{"issue":"4","key":"3361_CR17","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/bf00560341","volume":"7","author":"DJ Greenblatt","year":"1974","unstructured":"Greenblatt DJ, Koch-Weser J (1974) Clinical toxicity of chlordiazepoxide and diazepam in relation to serum albumin concentration: a report from the Boston Collaborative Drug Surveillance Program. Eur J Clin Pharmacol 7(4):259\u2013262. https:\/\/doi.org\/10.1007\/bf00560341","journal-title":"Eur J Clin Pharmacol"},{"issue":"5\u20136","key":"3361_CR18","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1159\/000090185","volume":"28","author":"C Haller","year":"2005","unstructured":"Haller C (2005) Hypoalbuminemia in renal failure: pathogenesis and therapeutic considerations. Kidney Blood Press Res 28(5\u20136):307\u2013310. https:\/\/doi.org\/10.1159\/000090185","journal-title":"Kidney Blood Press Res"},{"issue":"5","key":"3361_CR19","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1007\/s12072-021-10203-9","volume":"15","author":"L Hartl","year":"2021","unstructured":"Hartl L, Jachs M, Desbalmes C et al (2021a) The differential activation of cardiovascular hormones across distinct stages of portal hypertension predicts clinical outcomes. Hepatol Int 15(5):1160\u20131173. https:\/\/doi.org\/10.1007\/s12072-021-10203-9","journal-title":"Hepatol Int"},{"key":"3361_CR20","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11121264","author":"L Hartl","year":"2021","unstructured":"Hartl L, Jachs M, Simbrunner B et al (2021b) Cirrhosis-associated RAS-inflammation-coagulation axis anomalies: parallels to severe COVID-19. J Pers Med. https:\/\/doi.org\/10.3390\/jpm11121264","journal-title":"J Pers Med"},{"key":"3361_CR21","doi-asserted-by":"publisher","first-page":"872","DOI":"10.17179\/excli2016-863","volume":"15","author":"R Hassan","year":"2016","unstructured":"Hassan R (2016) Possibilities and limitations of intravital imaging. Excli J 15:872\u2013874. https:\/\/doi.org\/10.17179\/excli2016-863","journal-title":"Excli J"},{"issue":"1","key":"3361_CR22","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1002\/hep4.1797","volume":"6","author":"CH Holland","year":"2022","unstructured":"Holland CH, Ramirez Flores RO, Myllys M et al (2022) Transcriptomic cross-species analysis of chronic liver disease reveals consistent regulation between humans and mice. Hepatol Commun 6(1):161\u2013177. https:\/\/doi.org\/10.1002\/hep4.1797","journal-title":"Hepatol Commun"},{"key":"3361_CR23","first-page":"489","volume":"56","author":"IARC","year":"1993","unstructured":"IARC (1993) Ochratoxin A. IARC Monogr Eval Carcinog Risks Hum 56:489\u2013521","journal-title":"IARC Monogr Eval Carcinog Risks Hum"},{"issue":"4","key":"3361_CR24","first-page":"599","volume":"69","author":"M Kanisawa","year":"1978","unstructured":"Kanisawa M, Suzuki S (1978) Induction of renal and hepatic tumors in mice by ochratoxin A, a mycotoxin. Gan 69(4):599\u2013600","journal-title":"Gan"},{"key":"3361_CR25","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.633925","volume":"9","author":"S Koeppert","year":"2021","unstructured":"Koeppert S, Ghallab A, Peglow S et al (2021) Live imaging of calciprotein particle clearance and receptor mediated uptake: role of calciprotein monomers. Front Cell Dev Biol 9:633925. https:\/\/doi.org\/10.3389\/fcell.2021.633925","journal-title":"Front Cell Dev Biol"},{"issue":"3","key":"3361_CR26","first-page":"1507","volume":"279","author":"M Kontaxi","year":"1996","unstructured":"Kontaxi M, Echkardt U, Hagenbuch B, Stieger B, Meier PJ, Petzinger E (1996) Uptake of the mycotoxin ochratoxin A in liver cells occurs via the cloned organic anion transporting polypeptide. J Pharmacol Exp Ther 279(3):1507\u20131513","journal-title":"J Pharmacol Exp Ther"},{"issue":"10","key":"3361_CR27","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/0278-6915(85)90112-7","volume":"23","author":"S Kumagai","year":"1985","unstructured":"Kumagai S (1985) Ochratoxin A: plasma concentration and excretion into bile and urine in albumin-deficient rats. Food Chem Toxicol 23(10):941\u2013943. https:\/\/doi.org\/10.1016\/0278-6915(85)90112-7","journal-title":"Food Chem Toxicol"},{"issue":"4","key":"3361_CR28","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1002\/mnfr.200800149","volume":"53","author":"A Mally","year":"2009","unstructured":"Mally A, Dekant W (2009) Mycotoxins and the kidney: modes of action for renal tumor formation by ochratoxin A in rodents. Mol Nutr Food Res 53(4):467\u2013478. https:\/\/doi.org\/10.1002\/mnfr.200800149","journal-title":"Mol Nutr Food Res"},{"key":"3361_CR29","doi-asserted-by":"publisher","first-page":"299","DOI":"10.3389\/fphys.2014.00299","volume":"5","author":"AM Merlot","year":"2014","unstructured":"Merlot AM, Kalinowski DS, Richardson DR (2014) Unraveling the mysteries of serum albumin-more than just a serum protein. Front Physiol 5:299. https:\/\/doi.org\/10.3389\/fphys.2014.00299","journal-title":"Front Physiol"},{"issue":"1","key":"3361_CR30","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s12550-016-0261-y","volume":"33","author":"K Mu\u00f1oz","year":"2017","unstructured":"Mu\u00f1oz K, Cramer B, Dopstadt J, Humpf HU, Degen GH (2017) Evidence of ochratoxin A conjugates in urine samples from infants and adults. Mycotoxin Res 33(1):39\u201347. https:\/\/doi.org\/10.1007\/s12550-016-0261-y","journal-title":"Mycotoxin Res"},{"issue":"1","key":"3361_CR31","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1080\/10408440590905948","volume":"35","author":"E O'Brien","year":"2005","unstructured":"O\u2019Brien E, Dietrich DR (2005) Ochratoxin A: the continuing enigma. Crit Rev Toxicol 35(1):33\u201360. https:\/\/doi.org\/10.1080\/10408440590905948","journal-title":"Crit Rev Toxicol"},{"issue":"1","key":"3361_CR32","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1073\/pnas.1017547108","volume":"108","author":"CH \u00d6sterreicher","year":"2011","unstructured":"\u00d6sterreicher CH, Penz-\u00d6sterreicher M, Grivennikov SI et al (2011) Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver. Proc Natl Acad Sci U S A 108(1):308\u2013313. https:\/\/doi.org\/10.1073\/pnas.1017547108","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"31","key":"3361_CR33","doi-asserted-by":"publisher","first-page":"7884","DOI":"10.1021\/jp034783x","volume":"107","author":"JL Perry","year":"2003","unstructured":"Perry JL, Christensen T, Goldsmith MR, Toone EJ, Beratan DN, Simon JD (2003) Binding of ochratoxin A to human serum albumin stabilized by a protein\u2212ligand ion pair. J Phys Chem B 107(31):7884\u20137888. https:\/\/doi.org\/10.1021\/jp034783x","journal-title":"J Phys Chem B"},{"issue":"8677","key":"3361_CR34","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1016\/s0140-6736(89)92042-4","volume":"2","author":"A Phillips","year":"1989","unstructured":"Phillips A, Shaper AG, Whincup PH (1989) Association between serum albumin and mortality from cardiovascular disease, cancer, and other causes. Lancet 2(8677):1434\u20131436. https:\/\/doi.org\/10.1016\/s0140-6736(89)92042-4","journal-title":"Lancet"},{"issue":"5","key":"3361_CR35","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1002\/bio.2423","volume":"28","author":"M Poor","year":"2013","unstructured":"Poor M, Kunsagi-Mate S, Czibulya Z et al (2013) Fluorescence spectroscopic investigation of competitive interactions between ochratoxin A and 13 drug molecules for binding to human serum albumin. Luminescence 28(5):726\u2013733. https:\/\/doi.org\/10.1002\/bio.2423","journal-title":"Luminescence"},{"issue":"3","key":"3361_CR36","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1007\/s00204-016-1906-5","volume":"91","author":"R Reif","year":"2017","unstructured":"Reif R, Ghallab A, Beattie L et al (2017) In vivo imaging of systemic transport and elimination of xenobiotics and endogenous molecules in mice. Arch Toxicol 91(3):1335\u20131352. https:\/\/doi.org\/10.1007\/s00204-016-1906-5","journal-title":"Arch Toxicol"},{"issue":"12","key":"3361_CR37","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.1007\/s00277-016-2795-7","volume":"95","author":"SN Reiss","year":"2016","unstructured":"Reiss SN, Buie LW, Adel N, Goldman DA, Devlin SM, Douer D (2016) Hypoalbuminemia is significantly associated with increased clearance time of high dose methotrexate in patients being treated for lymphoma or leukemia. Ann Hematol 95(12):2009\u20132015. https:\/\/doi.org\/10.1007\/s00277-016-2795-7","journal-title":"Ann Hematol"},{"issue":"5","key":"3361_CR38","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1002\/hep.32289","volume":"75","author":"J Remetic","year":"2022","unstructured":"Remetic J, Ghallab A, Hobloss Z et al (2022) Loss of bile salt export pump aggravates lipopolysaccharide-induced liver injury in mice due to impaired hepatic endotoxin clearance. Hepatology 75(5):1095\u20131109. https:\/\/doi.org\/10.1002\/hep.32289","journal-title":"Hepatology"},{"issue":"1","key":"3361_CR39","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.cbi.2005.10.106","volume":"159","author":"D Ringot","year":"2006","unstructured":"Ringot D, Chango A, Schneider YJ, Larondelle Y (2006) Toxicokinetics and toxicodynamics of ochratoxin A, an update. Chem Biol Interact 159(1):18\u201346. https:\/\/doi.org\/10.1016\/j.cbi.2005.10.106","journal-title":"Chem Biol Interact"},{"issue":"1","key":"3361_CR40","doi-asserted-by":"publisher","first-page":"6224","DOI":"10.1038\/s41598-017-04574-z","volume":"7","author":"A Schenk","year":"2017","unstructured":"Schenk A, Ghallab A, Hofmann U et al (2017) Physiologically-based modelling in mice suggests an aggravated loss of clearance capacity after toxic liver damage. Sci Rep 7(1):6224. https:\/\/doi.org\/10.1038\/s41598-017-04574-z","journal-title":"Sci Rep"},{"issue":"9","key":"3361_CR41","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1038\/s42255-021-00452-1","volume":"3","author":"KM Schneider","year":"2021","unstructured":"Schneider KM, Candels LS, Hov JR et al (2021a) Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling. Nat Metab 3(9):1228\u20131241. https:\/\/doi.org\/10.1038\/s42255-021-00452-1","journal-title":"Nat Metab"},{"issue":"4","key":"3361_CR42","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/j.jcmgh.2020.11.002","volume":"11","author":"KM Schneider","year":"2021","unstructured":"Schneider KM, Elfers C, Ghallab A et al (2021b) Intestinal dysbiosis amplifies acetaminophen-induced acute liver injury. Cell Mol Gastroenterol Hepatol 11(4):909\u2013933. https:\/\/doi.org\/10.1016\/j.jcmgh.2020.11.002","journal-title":"Cell Mol Gastroenterol Hepatol"},{"issue":"9","key":"3361_CR43","doi-asserted-by":"publisher","first-page":"2963","DOI":"10.1007\/s00204-018-2271-3","volume":"92","author":"S Sezgin","year":"2018","unstructured":"Sezgin S, Hassan R, Zuhlke S et al (2018) Spatio-temporal visualization of the distribution of acetaminophen as well as its metabolites and adducts in mouse livers by MALDI MSI. Arch Toxicol 92(9):2963\u20132977. https:\/\/doi.org\/10.1007\/s00204-018-2271-3","journal-title":"Arch Toxicol"},{"issue":"2","key":"3361_CR44","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1002\/jpen.1451","volume":"43","author":"PB Soeters","year":"2019","unstructured":"Soeters PB, Wolfe RR, Shenkin A (2019) Hypoalbuminemia: pathogenesis and clinical significance. JPEN J Parenter Enteral Nutr 43(2):181\u2013193. https:\/\/doi.org\/10.1002\/jpen.1451","journal-title":"JPEN J Parenter Enteral Nutr"},{"key":"3361_CR45","doi-asserted-by":"publisher","DOI":"10.3390\/toxins10070256","author":"F Sueck","year":"2018","unstructured":"Sueck F, Poor M, Faisal Z et al (2018) Interaction of ochratoxin A and its thermal degradation product 2\u2019R-ochratoxin A with human serum albumin. Toxins (basel). https:\/\/doi.org\/10.3390\/toxins10070256","journal-title":"Toxins (basel)"},{"issue":"1","key":"3361_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12550-019-00360-0","volume":"36","author":"F Sueck","year":"2020","unstructured":"Sueck F, Specht J, Cramer B, Humpf HU (2020) Identification of ochratoxin-N-acetyl-L-cysteine as a new ochratoxin A metabolite and potential biomarker in human urine. Mycotoxin Res 36(1):1\u201310. https:\/\/doi.org\/10.1007\/s12550-019-00360-0","journal-title":"Mycotoxin Res"},{"key":"3361_CR47","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.fct.2018.01.002","volume":"112","author":"Y Tao","year":"2018","unstructured":"Tao Y, Xie S, Xu F et al (2018) Ochratoxin A: toxicity, oxidative stress and metabolism. Food Chem Toxicol 112:320\u2013331. https:\/\/doi.org\/10.1016\/j.fct.2018.01.002","journal-title":"Food Chem Toxicol"},{"issue":"1","key":"3361_CR48","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1109\/83.650848","volume":"7","author":"P Th\u00e9venaz","year":"1998","unstructured":"Th\u00e9venaz P, Ruttimann UE, Unser M (1998) A pyramid approach to subpixel registration based on intensity. IEEE Trans Image Process: Publ IEEE Signal Process Soc 7(1):27\u201341. https:\/\/doi.org\/10.1109\/83.650848","journal-title":"IEEE Trans Image Process: Publ IEEE Signal Process Soc"},{"issue":"4","key":"3361_CR49","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1002\/jps.2600660402","volume":"66","author":"JJ Vallner","year":"1977","unstructured":"Vallner JJ (1977) Binding of drugs by albumin and plasma protein. J Pharm Sci 66(4):447\u2013465. https:\/\/doi.org\/10.1002\/jps.2600660402","journal-title":"J Pharm Sci"},{"issue":"4","key":"3361_CR50","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1002\/hep.31422","volume":"73","author":"N Vartak","year":"2021","unstructured":"Vartak N, Guenther G, Joly F et al (2021) Intravital dynamic and correlative imaging of mouse livers reveals diffusion-dominated canalicular and flow-augmented ductular bile flux. Hepatology 73(4):1531\u20131550. https:\/\/doi.org\/10.1002\/hep.31422","journal-title":"Hepatology"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-022-03361-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00204-022-03361-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-022-03361-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T19:07:31Z","timestamp":1664564851000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00204-022-03361-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,13]]},"references-count":50,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["3361"],"URL":"https:\/\/doi.org\/10.1007\/s00204-022-03361-8","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,13]]},"assertion":[{"value":"28 June 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}