{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T22:12:25Z","timestamp":1780870345700,"version":"3.54.1"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hyperglycemia significantly increases the production of reactive oxygen species (ROS), leading to amplified DNA damage and a higher potential for mutations. Pioglitazone, a thiazolidine\u2010class oral antidiabetic drug, enhances insulin sensitivity but also raises concerns about cancer risk due to ROS\u2010induced genotoxic effects. We hypothesized and evaluated the genotoxic potential of pioglitazone under hyperglycemic conditions using TK6 cells. Genotoxicity was assessed through the Chromosome Aberration (CA) assay and GADD45\u03b1 gene expression analysis, while cytotoxicity was measured by the Mitotic Index (MI) at doses of 25, 50, and 100\u2009\u00b5g\/mL of pioglitazone. Under glucose concentrations of 300, 400, and 500\u2009mg\/dL, pioglitazone did not significantly increase CA frequency or affect GADD45\u03b1 expression levels in TK6 cells. A decrease in MI at 100\u2009\u00b5g\/mL was observed. These findings indicate that pioglitazone does not exhibit genotoxic effects under hyperglycemic conditions.<\/jats:p>","DOI":"10.1002\/jbt.70332","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T12:59:38Z","timestamp":1749041978000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Investigating the Genotoxic Potential of Pioglitazone in Hyperglycemic Conditions Using Chromosome Aberration and GADD45\u03b1 Markers in TK6 Cells"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4474-2594","authenticated-orcid":false,"given":"Darshan T.","family":"Valani","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Zydus Research Centre Zydus Lifesciences Limited Ahmedabad India"},{"name":"Gujarat Technological University Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8393-0016","authenticated-orcid":false,"given":"Dolatsinh B.","family":"Zala","sequence":"additional","affiliation":[{"name":"School of Applied Sciences and Technology (SAST) Scholar Gujarat Technological University Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7379-9277","authenticated-orcid":false,"given":"Chetan K.","family":"Kajavadara","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Zydus Research Centre Zydus Lifesciences Limited Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1227-7408","authenticated-orcid":false,"given":"Laxit K.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Zydus Research Centre Zydus Lifesciences Limited Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiren M.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Zydus Research Centre Zydus Lifesciences Limited Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Sundar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Zydus Research Centre Zydus Lifesciences Limited Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5730-1435","authenticated-orcid":false,"given":"Mukul R.","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Zydus Research Centre Zydus Lifesciences Limited Ahmedabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-024-00824-9"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.3251"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00094.2005"},{"key":"e_1_2_10_5_1","first-page":"160","article-title":"Oxidative Damage to DNA and Its Relationship With Diabetic Complications","volume":"20","author":"Pan H.\u2010Z.","year":"2007","journal-title":"Biomedical and Environmental Sciences: BES"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.3.375"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2017.32.2.241"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfp256"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.21275\/SR25105163035"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/dcS13-2031"},{"key":"e_1_2_10_11_1","unstructured":"Center for Drug Evaluation and Research. FDA Drug Safety Communication: Update to Ongoing Safety Review of Actos (Pioglitazone) and Increased Risk of Bladder Cancer [WWW Document] (2023).https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-drug-safety-communication-update-ongoing-safety-review-actos-pioglitazone-and-increased-risk."},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-1085-2542"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2007.01.006"},{"key":"e_1_2_10_14_1","volume-title":"Test No. 473: In Vitro Mammalian Chromosomal Aberration Test","year":"2016"},{"key":"e_1_2_10_15_1","unstructured":"ICH S2 (R1): Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use ICH (2012)."},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgn075"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2268"},{"key":"e_1_2_10_18_1","unstructured":"Actos (Pioglitazone Hydrochloride) Tablets Drug Approval Package [WWW Document] (1999).https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/99\/021073A_Actos.cfm."},{"key":"e_1_2_10_19_1","unstructured":"ACTOS\u2122 (Pioglitazone Hydrochloride) Tablets NDA No. 21\u2010073 \u2010 Label (n.d.)."},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22424"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.09.017"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/geac025"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004199"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.4172\/1948-5956.1000265"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfaa035"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-9-82"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00545"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70332","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70332","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70332","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:21:19Z","timestamp":1771338079000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/jbt.70332"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70332","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2025-04-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70332"}}