{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T04:43:23Z","timestamp":1761972203406,"version":"build-2065373602"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology Letters"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.toxlet.2025.111733","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T22:33:57Z","timestamp":1759012437000},"page":"111733","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Pre-clinical safety assessments of gadobutrol in diabetes-induced neuropathy: In vivo, in vitro and in silico studies"],"prefix":"10.1016","volume":"413","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-1783","authenticated-orcid":false,"given":"Batuhan","family":"Bilgin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Munevver Gizem","family":"Hekim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammed","family":"Adam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferah","family":"Bulut","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seval Ulku","family":"Orhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suat","family":"Tekin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet Tahir","family":"Husunet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mete","family":"Ozcan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.toxlet.2025.111733_bib1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1148\/radiol.2021210892","article-title":"Effects of gadolinium deposition in the brain on motor or behavioral function: a mouse model","volume":"301","author":"Akai","year":"2021","journal-title":"Radiology"},{"key":"10.1016\/j.toxlet.2025.111733_bib2","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1080\/01480545.2021.1957913","article-title":"Genotoxic effects of gadobutrol and gadoversetamide active substances used in magnetic resonance imaging in human peripheral lymphocytes in vitro","volume":"45","author":"Akbas","year":"2022","journal-title":"Drug Chem. Toxicol."},{"key":"10.1016\/j.toxlet.2025.111733_bib3","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1148\/radiol.2020192645","article-title":"Gadolinium retention in the central and peripheral nervous system: implications for pain, cognition, and neurogenesis","volume":"297","author":"Alkhunizi","year":"2020","journal-title":"Radiology"},{"key":"10.1016\/j.toxlet.2025.111733_bib4","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1097\/RLI.0000000000000884","article-title":"Different impact of gadopentetate and gadobutrol on inflammation-promoted retention and toxicity of gadolinium within the mouse brain","volume":"57","author":"Anderhalten","year":"2022","journal-title":"Invest. Radiol."},{"key":"10.1016\/j.toxlet.2025.111733_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.neulet.2019.134295","article-title":"Effects of gadolinium and gadolinium chelates on intracellular calcium signaling in sensory neurons","volume":"707","author":"Baykara","year":"2019","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.toxlet.2025.111733_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbadis.2023.166932","article-title":"The role of RLIP76 in oxidative stress and mitochondrial dysfunction: evidence based on autopsy brains from Alzheimer's disease patients","volume":"1870","author":"Bose","year":"2024","journal-title":"Biochim. et Biophys. Acta Mol. basis Dis."},{"key":"10.1016\/j.toxlet.2025.111733_bib7","doi-asserted-by":"crossref","DOI":"10.1148\/radiol.231984","article-title":"Gadolinium presence in rat skin: assessment of histopathologic changes associated with small fiber neuropathy","volume":"310","author":"Boyken","year":"2024","journal-title":"Radiology"},{"key":"10.1016\/j.toxlet.2025.111733_bib8","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/414813a","article-title":"Biochemistry and molecular cell biology of diabetic complications","volume":"414","author":"Brownlee","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.toxlet.2025.111733_bib9","doi-asserted-by":"crossref","DOI":"10.1002\/jmri.29347","article-title":"Editorial for \"effects of gadolinium retention in the brains of type 2 diabetic rats after repeated administration of gadolinium-based MRI contrast agents on neurobiology and NLRP3 inflammasome activation\"","author":"Chaganti","year":"2024","journal-title":"J. Magn. Reson. Imaging: JMRI"},{"key":"10.1016\/j.toxlet.2025.111733_bib10","doi-asserted-by":"crossref","first-page":"E132","DOI":"10.1152\/ajpendo.00620.2014","article-title":"Mitochondrial transcription factor a regulation of mitochondrial degeneration in experimental diabetic neuropathy","volume":"309","author":"Chandrasekaran","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.toxlet.2025.111733_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2024.111514","article-title":"Pramipexole protects against diabetic neuropathy: effect on oxidative stress, TLR4\/IRAK-1\/TRAF-6\/NF-\u03baB and downstream inflammatory mediators","volume":"128","author":"Eisa","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.toxlet.2025.111733_bib12","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/2251-6581-12-60","article-title":"Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans","volume":"12","author":"Eleazu","year":"2013","journal-title":"J. Diabetes Metab. Disord."},{"key":"10.1016\/j.toxlet.2025.111733_bib13","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1097\/RLI.0000000000000462","article-title":"10 years of nephrogenic systemic fibrosis: a comprehensive analysis of nephrogenic systemic fibrosis reports received by a pharmaceutical company from 2006 to 2016","volume":"53","author":"Endrikat","year":"2018","journal-title":"Invest. Radiol."},{"key":"10.1016\/j.toxlet.2025.111733_bib14","article-title":"Clinical safety of gadobutrol: review of over 25 years of use exceeding 100 million administrations","author":"Endrikat","year":"2024","journal-title":"Invest. Radiol."},{"key":"10.1016\/j.toxlet.2025.111733_bib15","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.neuron.2017.02.005","article-title":"New horizons in diabetic neuropathy: mechanisms, bioenergetics, and pain","volume":"93","author":"Feldman","year":"2017","journal-title":"Neuron"},{"key":"10.1016\/j.toxlet.2025.111733_bib16","article-title":"The Mas-related g protein-coupled receptor d (Mrgprd) mediates pain hypersensitivity in painful diabetic neuropathy","author":"George","year":"2023","journal-title":"Pain"},{"key":"10.1016\/j.toxlet.2025.111733_bib17","first-page":"1","article-title":"Diabetes: a review of its pathophysiology, and advanced methods of mitigation","author":"Gupta","year":"2024","journal-title":"Curr. Med. Res. Opin."},{"key":"10.1016\/j.toxlet.2025.111733_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.bej.2020.107758","article-title":"Determination of the pH-dependent immobilization efficacy of \u03b1-glycosidase and its catalytic performance on SnO2: Sb\/ITO thin films","volume":"163","author":"G\u00fcr","year":"2020","journal-title":"Biochem. Eng. J."},{"key":"10.1016\/j.toxlet.2025.111733_bib19","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/mrm.29443","article-title":"Gadolinium retention in the ischemic cerebrum: implications for pain, neuron loss, and neurological deficits","volume":"89","author":"Huang","year":"2023","journal-title":"Magn. Reson. Med."},{"key":"10.1016\/j.toxlet.2025.111733_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2020.139567","article-title":"Catalase and superoxide dismutase response and the underlying molecular mechanism for naphthalene","volume":"736","author":"Jing","year":"2020","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.toxlet.2025.111733_bib21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/RLI.0000000000000242","article-title":"Signal increase on unenhanced T1-weighted images in the rat brain after repeated, extended doses of gadolinium-based contrast agents: comparison of linear and macrocyclic agents","volume":"51","author":"Jost","year":"2016","journal-title":"Invest. Radiol."},{"key":"10.1016\/j.toxlet.2025.111733_bib22","doi-asserted-by":"crossref","first-page":"8669","DOI":"10.1007\/s11033-012-1722-9","article-title":"Evaluation of oxidative stress markers in pathogenesis of diabetic neuropathy","volume":"39","author":"Kasznicki","year":"2012","journal-title":"Mol. Biol. Rep."},{"key":"10.1016\/j.toxlet.2025.111733_bib23","doi-asserted-by":"crossref","DOI":"10.2174\/1573399819666230413094200","article-title":"Prevalence of diabetes in India: a review of IDF diabetes Atlas 10th edition","volume":"20","author":"Kumar","year":"2024","journal-title":"Curr. Diabetes Rev."},{"key":"10.1016\/j.toxlet.2025.111733_bib24","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/2053149","article-title":"CGRP reduces apoptosis of DRG cells induced by high-glucose oxidative stress injury through PI3K\/AKT induction of heme oxygenase-1 and Nrf-2 expression","volume":"2019","author":"Liu","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.toxlet.2025.111733_bib25","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1097\/RLI.0000000000000344","article-title":"Histology and gadolinium distribution in the rodent brain after the administration of cumulative high doses of linear and macrocyclic gadolinium-based contrast agents","volume":"52","author":"Lohrke","year":"2017","journal-title":"Invest. Radiol."},{"year":"2021","series-title":"IDF Diabetes Atlas","author":"Magliano","key":"10.1016\/j.toxlet.2025.111733_bib26"},{"key":"10.1016\/j.toxlet.2025.111733_bib27","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1148\/radiol.2018181151","article-title":"Gadolinium retention: a research roadmap from the 2018 NIH\/ACR\/RSNA workshop on gadolinium chelates","volume":"289","author":"McDonald","year":"2018","journal-title":"Radiology"},{"key":"10.1016\/j.toxlet.2025.111733_bib28","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/00044067-200401000-00012","article-title":"Diabetes and peripheral sensory neurons: what we don't know and how it can hurt us","volume":"15","author":"McHugh","year":"2004","journal-title":"AACN Clin. Issues"},{"key":"10.1016\/j.toxlet.2025.111733_bib29","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1111\/cns.14249","article-title":"Arctigenin improves neuropathy via ameliorating apoptosis and modulating autophagy in streptozotocin-induced diabetic mice","volume":"29","author":"Medras","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"10.1016\/j.toxlet.2025.111733_bib30","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1080\/10715762.2021.1914335","article-title":"Reactive oxygen species: the root cause of nanoparticle-induced toxicity in drosophila melanogaster","volume":"55","author":"Mishra","year":"2021","journal-title":"Free Radic. Res."},{"key":"10.1016\/j.toxlet.2025.111733_bib31","article-title":"Red blood cells as biomarkers and mediators in complications of diabetes mellitus: a review","volume":"103","author":"Obeagu","year":"2024","journal-title":"Medicine"},{"key":"10.1016\/j.toxlet.2025.111733_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2021.107654","article-title":"Evaluation of oxidant and intracellular anti-oxidant activity in rheumatoid arthritis patients: in vivo and in silico studies","volume":"97","author":"O\u011ful","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.toxlet.2025.111733_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2024.e26863","article-title":"A systematic review of astragaloside IV effects on animal models of diabetes mellitus and its complications","volume":"10","author":"Qu","year":"2024","journal-title":"Heliyon"},{"key":"10.1016\/j.toxlet.2025.111733_bib34","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/RLI.0000000000000677","article-title":"Is small fiber neuropathy induced by gadolinium-based contrast agents?","volume":"55","author":"Radbruch","year":"2020","journal-title":"Invest. Radiol."},{"key":"10.1016\/j.toxlet.2025.111733_bib35","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","article-title":"Dose translation from animal to human studies revisited","volume":"22","author":"Reagan-Shaw","year":"2008","journal-title":"FASEB J.: Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"10.1016\/j.toxlet.2025.111733_bib36","doi-asserted-by":"crossref","DOI":"10.3390\/ijms231911368","article-title":"Gadolinium accumulation and toxicity on in vitro grown stevia rebaudiana: a case-study on gadobutrol","volume":"23","author":"Scurtu","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.toxlet.2025.111733_bib37","doi-asserted-by":"crossref","first-page":"10741","DOI":"10.1002\/jcp.27748","article-title":"Agomelatine modulates calcium signaling through protein kinase c and phospholipase C-mediated mechanisms in rat sensory neurons","volume":"234","author":"Serhatlioglu","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.toxlet.2025.111733_bib38","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1097\/RLI.0000000000000880","article-title":"Use of real-life safety data from international pharmacovigilance databases to assess the importance of symptoms associated with gadolinium exposure","volume":"57","author":"Shahid","year":"2022","journal-title":"Invest. Radiol."},{"key":"10.1016\/j.toxlet.2025.111733_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.brainres.2020.147256","article-title":"Repeated gadoteric acid and gadobutrol exposure causes deterioration of behavior and memory functions in rats: MRI, histopathological and biochemical evidence","volume":"1754","author":"Solmaz","year":"2021","journal-title":"Brain Res."},{"key":"10.1016\/j.toxlet.2025.111733_bib40","doi-asserted-by":"crossref","first-page":"726","DOI":"10.2337\/diabetes.53.3.726","article-title":"Uncoupling proteins prevent glucose-induced neuronal oxidative stress and programmed cell death","volume":"53","author":"Vincent","year":"2004","journal-title":"Diabetes"},{"key":"10.1016\/j.toxlet.2025.111733_bib41","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1097\/RLI.0b013e318263f128","article-title":"Toxicological safety evaluation of gadobutrol","volume":"47","author":"Wack","year":"2012","journal-title":"Invest. Radiol."},{"key":"10.1016\/j.toxlet.2025.111733_bib42","doi-asserted-by":"crossref","first-page":"3535769","DOI":"10.1155\/2018\/3535769","article-title":"Exposure of macrophages to low-dose gadolinium-based contrast medium: impact on oxidative stress and cytokines production","volume":"2018","author":"Weng","year":"2018","journal-title":"Contrast Media Mol. Imaging"},{"key":"10.1016\/j.toxlet.2025.111733_bib43","first-page":"181","article-title":"Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic \u03b2 cell glucotoxicity","volume":"8","author":"Wu","year":"2015","journal-title":"Diabetes Metab. Syndr. Obes.: Target. Ther."},{"key":"10.1016\/j.toxlet.2025.111733_bib44","doi-asserted-by":"crossref","DOI":"10.3791\/51608-v","article-title":"The sciatic nerve cuffing model of neuropathic pain in mice","author":"Yalcin","year":"2014","journal-title":"J. Vis. Exp.: JoVE"},{"key":"10.1016\/j.toxlet.2025.111733_bib45","doi-asserted-by":"crossref","DOI":"10.1002\/jmri.29313","article-title":"Effects of gadolinium retention in the brains of type 2 diabetic rats after repeated administration of gadolinium-based MRI contrast agents on neurobiology and NLRP3 inflammasome activation","author":"Yao","year":"2024","journal-title":"J. Magn. Reson. Imaging: JMRI"}],"container-title":["Toxicology Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378427425026797?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378427425026797?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T03:32:45Z","timestamp":1761967965000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378427425026797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":45,"alternative-id":["S0378427425026797"],"URL":"https:\/\/doi.org\/10.1016\/j.toxlet.2025.111733","relation":{},"ISSN":["0378-4274"],"issn-type":[{"type":"print","value":"0378-4274"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pre-clinical safety assessments of gadobutrol in diabetes-induced neuropathy: In vivo, in vitro and in silico studies","name":"articletitle","label":"Article Title"},{"value":"Toxicology Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.toxlet.2025.111733","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"111733"}}