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Previous studies have reported that obtusifolin (OBS) exhibits several pharmacological effects, including antioxidant and antidiabetic activities. In this study, we investigated the protective effects of OBS against CIS-induced hepatonephrotoxicity. OBS (0.5 and 1\u00a0mg\/kg, i.p.) was administered to male mice for 10\u00a0days, while CIS (20\u00a0mg\/kg, i.p.) was administered on day 7 to induce hepatonephrotoxicity. The results showed that OBS reduced the CIS-induced elevations in AST, ALT, ALP, BUN, and creatinine levels by approximately 14%, 11%, 9%, 18%, and 14%, respectively. OBS also decreased liver and kidney MDA levels by approximately 31% and 25%, while enhancing liver and kidney GSH, SOD, and CAT levels by 50\u201336%, 80\u201370%, and 95\u201355%, respectively. In association with oxidative stress and the apoptotic process, OBS reduced liver and kidney mRNA expression levels of Nrf2 (by approximately 1.7- and 1.6-fold, respectively), HO-1 (by 1.6- and 1.4-fold, respectively), and Bcl-2 (by 1.6- and 1.4-fold, respectively). Additionally, OBS suppressed the mRNA expression levels of NF-\u03baB (by 0.7- and 0.7-fold), TNF-\u03b1 (by 0.6- and 0.6-fold), Bax (by 0.8- and 0.7-fold), and Cas-3 (by 0.7- and 0.7-fold). Protein expression analysis revealed that OBS increased Nrf2 (showing a 1.7- to 1.2-fold) and Bcl-2 levels (by 1.3- to 1.8-fold), and reduced Bax (by 0.7- to 0.8-fold) and caspase-3 (by 0.7- and 0.7-fold) levels altered by CIS treatment. Histopathological examinations confirmed that OBS reduced liver and kidney damage caused by CIS. In conclusion, OBS significantly improved CIS-induced hepatonephrotoxicity by reducing oxidative stress, inflammation, and apoptosis via modulation of the Nrf2\/HO-1 pathway. These findings suggest that OBS could be a potential therapeutic agent for mitigating the side effects of chemotherapeutics.<\/jats:p>","DOI":"10.1007\/s00210-025-03900-x","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T06:25:41Z","timestamp":1740032741000},"page":"10337-10352","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Obtusifolin improves cisplatin-induced hepatonephrotoxicity via the Nrf2\/HO-1 signaling pathway"],"prefix":"10.1007","volume":"398","author":[{"given":"Selcan","family":"Cesur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berrin","family":"Yalinbas-Kaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Tureyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahriye","family":"Zemheri-Navruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan Huseyin","family":"Demirel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinan","family":"Ince","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"3900_CR1","doi-asserted-by":"publisher","first-page":"136338","DOI":"10.1016\/J.SCITOTENV.2019.136338","volume":"710","author":"MM Abdel-Daim","year":"2020","unstructured":"Abdel-Daim MM, Abdel-Rahman HG, Dessouki AA et al (2020) Impact of garlic (Allium sativum) oil on cisplatin-induced hepatorenal biochemical and histopathological alterations in rats. 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