{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:42:37Z","timestamp":1788846157881,"version":"build-2803163510"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Chemotherapeutic agents used for most common cancers are frequently associated with neurotoxicity, which often include debilitating side effects such as seizures. Docetaxel, one of the most widely and effectively used chemotherapeutic drugs, is associated with an array of symptoms referred to as Docetaxel-Induced Peripheral Neuropathies (DIPNs), including motor neuropathy, tingling, muscle weakness, and numbness. In this study, we use the electroconvulsive assay to model DIPN-related muscle weakness in\n                    <jats:italic>C. elegans,<\/jats:italic>\n                    via shock induction\n                    <jats:italic>.<\/jats:italic>\n                    We show that acutely or chronically exposing nematodes to docetaxel increases time to recovery from shock-induced seizure-like behaviors. Additionally, we find that sildenafil citrate, a PDE-5 inhibitor, and a novel bicyclic bridge compound, Resveramorph-3 (RVM-3), are both effective at rescuing the animals from prolonged seizure-like movement duration following acute and chronic exposure to docetaxel. The results demonstrate that sildenafil citrate and RVM-3 are potential candidates for mitigating the neurological deficits resulting from DIPNs.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0342236","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T18:35:56Z","timestamp":1770402956000},"page":"e0342236","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Anticonvulsant effects of novel and repurposed drugs on docetaxel-induced neuropathy in C. elegans"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2887-0039","authenticated-orcid":true,"given":"Paola Ximena","family":"Gonzalez-Lerma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-6284","authenticated-orcid":true,"given":"Scarlet J.","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Dawson-Scully","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"pone.0342236.ref001","volume-title":"Cancer facts & figures 2025: Economic","author":"American Cancer Society","year":"2025"},{"issue":"3","key":"pone.0342236.ref002","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN Estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"15","key":"pone.0342236.ref003","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.2165\/00003495-200363150-00003","article-title":"Neurotoxic complications of chemotherapy in patients with cancer: Clinical signs and optimal management","volume":"63","author":"CCP Verstappen","year":"2003","journal-title":"Drugs"},{"key":"pone.0342236.ref004","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3389\/fnins.2017.00481","article-title":"A mechanistic understanding of axon degeneration in chemotherapy-induced peripheral neuropathy","volume":"11","author":"Y Fukuda","year":"2017","journal-title":"Front Neurosci"},{"issue":"7","key":"pone.0342236.ref005","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1586\/14737140.8.7.1023","article-title":"Docetaxel in the management of patients with head and neck squamous cell carcinoma","volume":"8","author":"J Bernier","year":"2008","journal-title":"Expert Rev Anticancer Ther"},{"issue":"3","key":"pone.0342236.ref006","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1177\/107327480601300306","article-title":"Novel agents and targets in managing patients with metastatic prostate cancer","volume":"13","author":"WW Tan","year":"2006","journal-title":"Cancer Control"},{"issue":"4","key":"pone.0342236.ref007","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1136\/jnnp.2006.106211","article-title":"Seizures and epilepsy in oncological practice: Causes, course, mechanisms and treatment","volume":"78","author":"G Singh","year":"2007","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0342236.ref008","first-page":"253","article-title":"Presentation and management of docetaxel-related adverse effects in patients with breast cancer","volume":"6","author":"MY Ho","year":"2014","journal-title":"Cancer Manag Res"},{"issue":"3","key":"pone.0342236.ref009","doi-asserted-by":"crossref","first-page":"251","DOI":"10.2165\/00044011-199917030-00010","article-title":"Transient Encephalopathy Followed by Seizures after Docetaxel Infusion","volume":"17","author":"A Polyzos","year":"1999","journal-title":"Clinical Drug Investigation"},{"issue":"1","key":"pone.0342236.ref010","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1212\/WNL.46.1.108","article-title":"Peripheral neuropathy secondary to docetaxel (Taxotere)","volume":"46","author":"PZ New","year":"1996","journal-title":"Neurology"},{"issue":"10","key":"pone.0342236.ref011","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1016\/j.ejca.2005.04.006","article-title":"Morphological and morphometric analysis of paclitaxel and docetaxel-induced peripheral neuropathy in rats","volume":"41","author":"E Persohn","year":"2005","journal-title":"Eur J Cancer"},{"issue":"1","key":"pone.0342236.ref012","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.neucli.2019.12.001","article-title":"Nerve conduction, circulating osteopontin and taxane-induced neuropathy in breast cancer patients","volume":"50","author":"C Pizzamiglio","year":"2020","journal-title":"Neurophysiol Clin"},{"issue":"3","key":"pone.0342236.ref013","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1159\/000507843","article-title":"Docetaxel-induced peripheral neuropathy in breast cancer patients treated with adjuvant or neo-adjuvant chemotherapy","volume":"16","author":"HL Cheng","year":"2021","journal-title":"Breast Care (Basel)"},{"issue":"3","key":"pone.0342236.ref014","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s12035-013-8434-6","article-title":"Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders","volume":"48","author":"C Bessa","year":"2013","journal-title":"Mol Neurobiol"},{"issue":"6","key":"pone.0342236.ref015","doi-asserted-by":"crossref","first-page":"311","DOI":"10.2131\/jts.48.311","article-title":"Evaluation of neurotoxicity of anticancer drugs using nematode Caenorhabditis elegans as a model organism","volume":"48","author":"Y Sakaguchi","year":"2023","journal-title":"J Toxicol Sci"},{"key":"pone.0342236.ref016","doi-asserted-by":"crossref","first-page":"113090","DOI":"10.1016\/j.expneurol.2019.113090","article-title":"Analyzing chemotherapy-induced peripheral neuropathy in vivo using non-mammalian animal models","volume":"323","author":"AM Cirrincione","year":"2020","journal-title":"Exp Neurol"},{"issue":"7","key":"pone.0342236.ref017","doi-asserted-by":"crossref","first-page":"993","DOI":"10.3390\/biom10070993","article-title":"Effects of NAD+ in caenorhabditis elegans models of neuronal damage","volume":"10","author":"Y Lee","year":"2020","journal-title":"Biomolecules"},{"issue":"1","key":"pone.0342236.ref018","doi-asserted-by":"crossref","first-page":"13655","DOI":"10.1038\/s41598-022-17537-w","article-title":"Roundup and glyphosate\u2019s impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegans","volume":"12","author":"AS Naraine","year":"2022","journal-title":"Sci Rep"},{"issue":"9","key":"pone.0342236.ref019","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0163786","article-title":"Modulating behavior in C. elegans using electroshock and antiepileptic drugs","volume":"11","author":"MG Risley","year":"2016","journal-title":"PLoS One"},{"issue":"9","key":"pone.0342236.ref020","doi-asserted-by":"crossref","DOI":"10.21769\/BioProtoc.2270","article-title":"Electroshock Induced Seizures in Adult C. elegans","volume":"7","author":"MG Risley","year":"2017","journal-title":"Bio Protoc"},{"issue":"11","key":"pone.0342236.ref021","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0260072","article-title":"O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 modulate seizure susceptibility in C. elegans","volume":"16","author":"N Suthakaran","year":"2021","journal-title":"PLoS One"},{"issue":"1","key":"pone.0342236.ref022","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1021\/acschemneuro.8b00577","article-title":"Resveratrol-inspired bridged bicyclic compounds: A new compound class for the protection of synaptic function from acute oxidative stress","volume":"10","author":"WL Bollinger","year":"2019","journal-title":"ACS Chem Neurosci"},{"key":"pone.0342236.ref023","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1242\/jeb.041319","article-title":"Controlling anoxic tolerance in adult Drosophila via the cGMP-PKG pathway","volume":"213","author":"K Dawson-Scully","year":"2010","journal-title":"J Exp Biol"},{"issue":"11","key":"pone.0342236.ref024","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1111\/epi.17769","article-title":"Bridged bicyclic compounds: Comprehending a novel compound class as potential anti-seizure agents","volume":"64","author":"SE Stilley","year":"2023","journal-title":"Epilepsia"},{"issue":"6","key":"pone.0342236.ref025","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1002\/ana.24951","article-title":"Chemotherapy-induced peripheral neuropathy: A current review","volume":"81","author":"NP Staff","year":"2017","journal-title":"Ann Neurol"},{"issue":"6","key":"pone.0342236.ref026","doi-asserted-by":"crossref","first-page":"585","DOI":"10.3390\/jpm11060585","article-title":"The potential role of sildenafil in cancer management through EPR augmentation","volume":"11","author":"M Haider","year":"2021","journal-title":"J Pers Med"},{"issue":"2","key":"pone.0342236.ref027","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00232-014-9757-6","article-title":"Docetaxel modulates the delayed rectifier potassium current (IK) and ATP-sensitive potassium current (IKATP) in human breast cancer cells","volume":"248","author":"T Sun","year":"2015","journal-title":"J Membr Biol"},{"issue":"1","key":"pone.0342236.ref028","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3349\/ymj.2010.51.1.82","article-title":"Effect of sildenafil on neuropathic pain and hemodynamics in rats","volume":"51","author":"LJ Huang","year":"2010","journal-title":"Yonsei Med J"},{"issue":"2","key":"pone.0342236.ref029","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s10158-018-0211-9","article-title":"egl-4 modulates electroconvulsive seizure duration in C. elegans","volume":"18","author":"MG Risley","year":"2018","journal-title":"Invert Neurosci"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0342236","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T18:36:04Z","timestamp":1770402964000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0342236"}},"subtitle":[],"editor":[{"given":"Michael","family":"Massiah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":29,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0342236","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]}}}