{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:12:32Z","timestamp":1790723552858,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Apilarnil, a relatively understudied bee\u2010derived product from drone larvae, has recently gained attention due to its diverse chemical content and biological activities. Imatinib, a selective tyrosine kinase inhibitor widely used in cancer treatment, is recognized for its effectiveness but is also associated with off\u2010target toxicities including disturbances in redox homeostasis. While previous studies have mainly focused on the roles of the key antioxidant enzymes glucose\u20106\u2010phosphate dehydrogenase (G6PD), 6\u2010phosphogluconate dehydrogenase (6PGD), glutathione reductase (GR), glutathione\u2010S transferase (GST) and thioredoxin reductase (TrxR1) in tumor resistance mechanisms, their inhibition in non\u2010cancerous cells may contribute systemic toxicity. This study investigated whether co\u2010administration of apilarnil could alleviate the inhibitory effects of imatinib on these enzymes\n                    <jats:italic>in vivo<\/jats:italic>\n                    . The secondary metabolite profile of apilarnil was characterized using liquid chromatography\u2013high resolution mass spectrometry (LC\u2010HRMS) revealing a richness in phenolic compounds, notably isorhamnetin, phenolidzin, ascorbic acid, liquiritigenin, leucoside, 3\u2010(4\u2010hydroxyphenyl) propionic acid and caffeic acid. Enzyme activity assays showed that imatinib significantly suppressed the activities of G6PD, 6PGD, GR, GST and TrxR1 compared to the control group. However, co\u2010treatment with apilarnil particularly at a dose of 400\u2009mg\/kg, markedly restored activities of these enzymes. Furthermore, molecular docking analysis was performed to assess the binding affinities and interaction profiles of imatinib with target enzymes, confirming its potent inhibitory potential and revealing distinct but comparable binding interactions. These findings suggest that apilarnil may exert a protective effect against imatinib\u2010induced toxicity by modulating disruptions in metabolic enzyme activities.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70798","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:09:48Z","timestamp":1774429788000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Effects of Apilarnil and Imatinib on GR\/GST\/TrxR1 Enzyme Activities and Pentose Phosphate Pathway Enzymes in Rats"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6801-6242","authenticated-orcid":false,"given":"Adnan","family":"Ayna","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Sciences and Arts Bingol University Bingol 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