{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:49:08Z","timestamp":1782380948858,"version":"3.54.5"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Maintaining viability and physiological function in kidney tissue slice cultures remains a major challenge for\n                      <jats:italic>ex vivo<\/jats:italic>\n                      renal models, primarily due to limited oxygen diffusion into the tissue interior. In this study, we investigated whether shaking culture could improve the maintenance of primary rat kidney tissue slices.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Rat kidney tissue slices (200\u00a0\u00b5m) were cultured under static or shaking conditions for up to 7\u00a0days. Tissue viability, histological features, renal transporter activity, nephrotoxic responses, and metabolomic profiles were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Shaking culture markedly improved tissue viability, as evidenced by sustained ATP levels over 7\u00a0days compared with static conditions. Histological analysis revealed partial preservation of epithelial polarity, indicated by the maintained apical localization of aquaporin 1. Transporter studies demonstrated that uptake activities of Oat1\/3 and Oct2 substrates were better preserved under shaking conditions. Furthermore, shaking-cultured slices enabled the evaluation of nephron segment\u2013specific injury, with cisplatin inducing tubular damage and puromycin or dasatinib affecting glomerular structures. Metabolomic analysis revealed distinct alterations in central carbon metabolism, including increased levels of tricarboxylic acid cycle intermediates, suggesting improved mitochondrial function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings demonstrate that shaking culture provides a simple and effective approach to improve the culture microenvironment, thereby improving the maintenance of viability and physiological function in kidney tissue slices. This system may serve as a useful platform for investigating renal pharmacokinetics and drug-induced kidney injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/ftox.2026.1838970","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:39:11Z","timestamp":1782380351000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Shaking culture improves physiological maintenance of primary rat kidney tissue slices"],"prefix":"10.3389","volume":"8","author":[{"given":"Moeno","family":"Kadoguchi","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University","place":["Kanazawa, Ishikawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Division of Pathology, National Institute of Health Sciences","place":["Kawasaki, Kanagawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Advanced Materials & Solutions Research Laboratory, Research Center, Mitsui Chemicals, Inc.","place":["Mobara-shi, Chiba, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiro","family":"Esashika","sequence":"additional","affiliation":[{"name":"Advanced Materials & Solutions Research Laboratory, Research Center, Mitsui Chemicals, Inc.","place":["Mobara-shi, Chiba, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Yang","sequence":"additional","affiliation":[{"name":"Cell Culture Solution Department, New Business Incubation Center, Mitsui Chemicals, Inc.","place":["Chuo-ku, Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, Keio University","place":["Tsuruoka, Yamagata, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikumi","family":"Tamai","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University","place":["Kanazawa, Ishikawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Arakawa","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University","place":["Kanazawa, Ishikawa, Japan"]},{"name":"Department of Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University","place":["Nagoya, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1248\/bpb.b21-00875","article-title":"Evaluation of platinum anticancer drug-induced kidney injury in primary culture of rat kidney tissue slices by using gas-permeable plates","volume":"45","author":"Arakawa","year":"2022","journal-title":"Biol. Pharm. Bull."},{"key":"B2","doi-asserted-by":"publisher","first-page":"101056","DOI":"10.1016\/j.dmpk.2025.101056","article-title":"Advanced in vitro evaluation of drug-induced kidney injury using microphysiological systems in drug discovery and development","volume":"61","author":"Arakawa","year":"2025","journal-title":"Drug Metab. Pharmacokinet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"687","DOI":"10.3851\/IMP2770","article-title":"Tenofovir alafenamide is not a substrate for renal organic anion transporters (oats) and does not exhibit oat-dependent cytotoxicity","volume":"19","author":"Bam","year":"2014","journal-title":"Antivir. Ther."},{"key":"B4","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/nrneph.2017.107","article-title":"Mitochondrial energetics in the kidney","volume":"13","author":"Bhargava","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"F847","DOI":"10.1152\/ajprenal.2000.278.5.F847","article-title":"Selective degradation of E-cadherin and dissolution of E-cadherin-catenin complexes in epithelial ischemia","volume":"278","author":"Bush","year":"2000","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1038\/s41467-019-09936-x","article-title":"Disruption of podocyte cytoskeletal biomechanics by dasatinib leads to nephrotoxicity","volume":"10","author":"Calizo","year":"2019","journal-title":"Nat. Commun."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.2353\/ajpath.2010.090610","article-title":"Organic cation transporter 2 mediates cisplatin-induced Oto- and nephrotoxicity and is a target for protective interventions","volume":"176","author":"Ciarimboli","year":"2010","journal-title":"Am. J. Pathol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"135","DOI":"10.2131\/fts.9.135","article-title":"Cryopreserved human hepatocytes culture optimization on polymethylpentene oxygen permeable membranes for drug screening purposes","volume":"9","author":"Danoy","year":"2022","journal-title":"Fundam. Toxicol. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1038\/nprot.2010.111","article-title":"Preparation and incubation of precision-cut liver and intestinal slices for application in drug metabolism and toxicity studies","volume":"5","author":"De Graaf","year":"2010","journal-title":"Nat. Protoc."},{"key":"B10","doi-asserted-by":"publisher","first-page":"7137","DOI":"10.3390\/ijms22137137","article-title":"Best practices and progress in precision-cut liver slice cultures","volume":"22","author":"Dewyse","year":"2021","journal-title":"IJMS"},{"key":"B11","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/clpt.2009.139","article-title":"Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity","volume":"86","author":"Filipski","year":"2009","journal-title":"Clin. Pharmacol. Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3109\/00498254.2012.728013","article-title":"Preparation and culture of precision-cut organ slices from human and animal","volume":"43","author":"Fisher","year":"2013","journal-title":"Xenobiotica"},{"key":"B13","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1093\/hmg\/11.6.651","article-title":"WT1 is a key regulator of podocyte function: reduced expression levels cause crescentic glomerulonephritis and mesangial sclerosis","volume":"11","author":"Guo","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.neuroscience.2015.07.086","article-title":"Organotypic brain slice cultures: a review","volume":"305","author":"Humpel","year":"2015","journal-title":"Neuroscience"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1007\/s42247-024-00822-x","article-title":"Microphysiological systems for realizing microenvironment that mimics human physiology\u2014functional material and its standardization applied to microfluidics","volume":"8","author":"Ito","year":"2025","journal-title":"Emergent Mater"},{"key":"B16","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1248\/bpb.b25-00572","article-title":"Evaluation of drug-induced kidney injury by primary culture of Rat kidney tissue slices using oxygen-permeable polyolefin plate with low drug adsorption","volume":"49","author":"Kadoguchi","year":"2026","journal-title":"Biol. Pharm. Bull."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1111\/cas.16112","article-title":"Salivary metabolomic biomarkers for non\u2010invasive lung cancer detection","volume":"115","author":"Kajiwara","year":"2024","journal-title":"Cancer Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1016\/j.bcp.2010.08.019","article-title":"Disruption of multidrug and toxin extrusion MATE1 potentiates cisplatin-induced nephrotoxicity","volume":"80","author":"Nakamura","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s12995-017-0158-5","article-title":"Assessment of long-term cultivated human precision-cut lung slices as an ex vivo system for evaluation of chronic cytotoxicity and functionality","volume":"12","author":"Neuhaus","year":"2017","journal-title":"J. Occup. Med. Toxicol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"810478","DOI":"10.3389\/ftox.2022.810478","article-title":"Accurate evaluation of hepatocyte metabolisms on a noble oxygen-permeable material with low sorption characteristics","volume":"4","author":"Nishikawa","year":"2022","journal-title":"Front. Toxicol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"21555","DOI":"10.1038\/s41598-024-72938-3","article-title":"Profiling of metabolic dysregulation in ovarian cancer tissues and biofluids","volume":"14","author":"Ohta","year":"2024","journal-title":"Sci. Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1016\/S0960-9822(01)00560-7","article-title":"WT1 regulates the expression of the major glomerular podocyte membrane protein Podocalyxin","volume":"11","author":"Palmer","year":"2001","journal-title":"Curr. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.ajpath.2021.10.020","article-title":"The challenge of long-term cultivation of human precision-cut lung slices","volume":"192","author":"Preu\u00df","year":"2022","journal-title":"Am J Pathol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3334","DOI":"10.4414\/smw.2012.13662","article-title":"New insights in acute kidney failure in the critically ill","volume":"142","author":"Ricci","year":"2012","journal-title":"Swiss Med. Wkly."},{"key":"B25","doi-asserted-by":"publisher","first-page":"F431","DOI":"10.1152\/ajprenal.00389.2004","article-title":"WT1-interacting protein and ZO-1 translocate into podocyte nuclei after puromycin aminonucleoside treatment","volume":"289","author":"Rico","year":"2005","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.phrs.2016.05.012","article-title":"Inhibition of OCT2, MATE1 and MATE2-K as a possible mechanism of drug interaction between pazopanib and cisplatin","volume":"110","author":"Sauzay","year":"2016","journal-title":"Pharmacol. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/j.yexcr.2012.02.028","article-title":"Apicobasal polarity in the kidney","volume":"318","author":"Schl\u00fcter","year":"2012","journal-title":"Exp. Cell Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"32087","DOI":"10.1038\/srep32087","article-title":"Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models","volume":"6","author":"Shen","year":"2016","journal-title":"Sci. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13036-023-00357-5","article-title":"Culture of vibrating microtome tissue slices as a 3D model in biomedical research","volume":"17","author":"Siwczak","year":"2023","journal-title":"J. Biol. Eng."},{"key":"B30","doi-asserted-by":"publisher","first-page":"100511","DOI":"10.1016\/j.dmpk.2023.100511","article-title":"New in vitro screening system to detect drug-induced liver injury using a culture plate with low drug sorption and high oxygen permeability","volume":"52","author":"Takemura","year":"2023","journal-title":"Drug Metab. Pharmacokinet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1007\/s11095-006-9196-x","article-title":"Renal transport of Adefovir, Cidofovir, and Tenofovir by SLC22A family members (hOAT1, hOAT3, and hOCT2)","volume":"24","author":"Uwai","year":"2007","journal-title":"Pharm. Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3044","DOI":"10.1097\/01.ASN.0000146687.99058.25","article-title":"The Major podocyte protein Nephrin is transcriptionally activated by the wilms\u2019 Tumor suppressor WT1","volume":"15","author":"Wagner","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1016\/j.freeradbiomed.2012.07.012","article-title":"NADPH oxidase-mediated upregulation of connexin43 contributes to podocyte injury","volume":"53","author":"Yan","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.bcp.2007.03.004","article-title":"Differential contribution of organic cation transporters, OCT2 and MATE1, in platinum agent-induced nephrotoxicity","volume":"74","author":"Yokoo","year":"2007","journal-title":"Biochem. Pharmacol."}],"container-title":["Frontiers in Toxicology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2026.1838970\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:39:12Z","timestamp":1782380352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2026.1838970\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":34,"alternative-id":["10.3389\/ftox.2026.1838970"],"URL":"https:\/\/doi.org\/10.3389\/ftox.2026.1838970","relation":{},"ISSN":["2673-3080"],"issn-type":[{"value":"2673-3080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]},"article-number":"1838970"}}