Çağlayan, CüneytEkinci, İzzettinGür, CihanAyna, AdnanBayav, İbrahimKandemir, Fatih Mehmet2025-07-092025-07-09202510956670https://dx.doi.org/10.1002/jbt.70373https://hdl.handle.net/20.500.12451/13229Diclofenac (DCL) is a broadly prescribed non-steroidal anti-inflammatory drug (NSAID) for pain management and has been linked to nephrotoxicity despite its therapeutic benefits. This study provides new insights into the palliative impacts of chrysin (CH) against DCL-induced kidney damage by modulating oxidative injury, endoplasmic reticulum (ER) stress and apoptosis. The rats were divided into five groups: the control group (Group 1), CH-only group (50 mg/kg, Group 2), DCL-only group (50 mg/kg, Group 3), DCL + CH (25 mg/kg, Group 4), and DCL + CH (50 mg/kg, Group 5). DCL injection led to significant renal damage marked by elevated serum urea, creatinine and malondialdehyde (MDA) levels, reduced glutathione (GSH) concentration, and decreased activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase and catalase). The mRNA expression levels of Ho-1 and Nrf2 were also suppressed. Additionally, DCL treatment triggered apoptosis as evidenced by increased expression of Bax and caspase-3 alongside decreased Bcl-2 expression. Furthermore, DCL induced ER stress was confirmed by upregulation of Perk, Ire1, Atf-6, and Grp78 transcription levels. Also, it was demonstrated that DCL treatment upregulated Mmp2 and Mmp9 levels. Treatment with CH significantly mitigated these adverse effects suggesting that CH effectively protects DCL-induced kidney toxicity by targeting multiple pathways. In summary, this study highlights the importance of CH as a promising therapeutic agent for alleviating kidney damage associated with DCL toxicity.eninfo:eu-repo/semantics/openAccessApoptosisChrysinDiclofenacEndoplasmic Reticulum StressNephrotoxicityArticle39610.1002/jbt.7037340534331105008864030WOS:001511056500001Q2