Tamarix honey phenolics attenuate cisplatin-induced kidney toxicity by inhibition of inflammation mediated IL-6/STAT3/TNF-α and oxidative stress-dependent Nrf2/caspase-3 apoptotic signaling pathways
IntroductionCisplatin (CIS) is a productive chemotherapeutic agent that is effective against a variety of cancer types. Its utilization is linked to acute kidney injury and other adverse consequences. Among its toxic effects are oxidative stress, apoptosis as well as inflammation. Saudi Tamarix hone...
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Frontiers Media S.A.
2025-07-01
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| author | Hanan Aati Sultan Y. Aati Hebatallah S. Bahr Asmaa Ramadan Abdel-Sattar Marwa Ahmed Embaby Ahmed M. Reda Ahmed M. Reda Usama Ramadan Abdelmohsen Usama Ramadan Abdelmohsen Gerhard Bringmann Hossam M. Hassan Hossam M. Hassan Mostafa A. Darwish |
| author_facet | Hanan Aati Sultan Y. Aati Hebatallah S. Bahr Asmaa Ramadan Abdel-Sattar Marwa Ahmed Embaby Ahmed M. Reda Ahmed M. Reda Usama Ramadan Abdelmohsen Usama Ramadan Abdelmohsen Gerhard Bringmann Hossam M. Hassan Hossam M. Hassan Mostafa A. Darwish |
| author_sort | Hanan Aati |
| collection | DOAJ |
| description | IntroductionCisplatin (CIS) is a productive chemotherapeutic agent that is effective against a variety of cancer types. Its utilization is linked to acute kidney injury and other adverse consequences. Among its toxic effects are oxidative stress, apoptosis as well as inflammation. Saudi Tamarix honey (STH) is a valuable product with plentiful nutritional and health benefits, demonstrating advantageous effects against inflammation and oxidative stress. Therefore, this study examined the potential of STH to prevent oxidative stress, apoptosis, inflammation, and kidney impairment that are induced by CIS in rats, pointing to the entanglement of the Nrf2, the caspase-3, and the IL-6/STAT3/TNF-α signaling pathways.MethodHistopathological examinations of the kidney were also used to evaluate cisplatin-induced nephrotoxicity. The rats received STH (50, 100 mg/kg) for 10 days and were challenged with a single dose of CIS (7 mg/kg) on day 7.ResultsCIS caused injury to the glomeruli and the tubules, increased lipid peroxidation, TNF-α, IL-6, cleaved caspase-3, and decreased cellular antioxidants in the kidneys of rats. STH effectively prevented tissue injury, and ameliorated oxidative stress, inflammatory markers, in addition to caspase-3 in CIS-administered rats. STH is rich with antioxidants, suppressed STAT3 protein expression, and upregulated Nrf2 in CIS-administered rats. In conclusion, STH mitigated CIS-induced kidney injury by reducing oxidative stress, suppressing STAT3 and caspase-3, inhibiting pro-inflammatory mediators, and enhancing Nrf2 signaling. On the other hand, metabolomic profiling proposed the presence of 15 metabolites belonging to the chemical classes, phenolic acids, flavonoids and sterols, where phenolic acids were the most abundant classes. |
| format | Article |
| id | doaj-art-68fcdee8c66340e084c3bcaf0d13fcc0 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-68fcdee8c66340e084c3bcaf0d13fcc02025-08-20T03:31:27ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.15848321584832Tamarix honey phenolics attenuate cisplatin-induced kidney toxicity by inhibition of inflammation mediated IL-6/STAT3/TNF-α and oxidative stress-dependent Nrf2/caspase-3 apoptotic signaling pathwaysHanan Aati0Sultan Y. Aati1Hebatallah S. Bahr2Asmaa Ramadan Abdel-Sattar3Marwa Ahmed Embaby4Ahmed M. Reda5Ahmed M. Reda6Usama Ramadan Abdelmohsen7Usama Ramadan Abdelmohsen8Gerhard Bringmann9Hossam M. Hassan10Hossam M. Hassan11Mostafa A. Darwish12Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi ArabiaDepartment of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef, EgyptDepartment of Pharmacology and toxicology, Faculty of Pharmacy, Nile Valley University Egypt, Fayoum, EgyptDepartment of Medical Biochemistry, Faculty of Medicine, Beni-Suef University, Beni-Suef, EgyptDepartment of Pharmacy, Kut University College, Al Kut, IraqDepartment of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr, Cairo, EgyptDeraya Center for Scientific Research, Deraya University, Minia, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, Egypt0Institute of Organic Chemistry, University of Würzburg, Am Hubland, Würzburg, GermanyDepartment of Pharmacy, Kut University College, Al Kut, Iraq1Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sphinx University, Assuit, EgyptIntroductionCisplatin (CIS) is a productive chemotherapeutic agent that is effective against a variety of cancer types. Its utilization is linked to acute kidney injury and other adverse consequences. Among its toxic effects are oxidative stress, apoptosis as well as inflammation. Saudi Tamarix honey (STH) is a valuable product with plentiful nutritional and health benefits, demonstrating advantageous effects against inflammation and oxidative stress. Therefore, this study examined the potential of STH to prevent oxidative stress, apoptosis, inflammation, and kidney impairment that are induced by CIS in rats, pointing to the entanglement of the Nrf2, the caspase-3, and the IL-6/STAT3/TNF-α signaling pathways.MethodHistopathological examinations of the kidney were also used to evaluate cisplatin-induced nephrotoxicity. The rats received STH (50, 100 mg/kg) for 10 days and were challenged with a single dose of CIS (7 mg/kg) on day 7.ResultsCIS caused injury to the glomeruli and the tubules, increased lipid peroxidation, TNF-α, IL-6, cleaved caspase-3, and decreased cellular antioxidants in the kidneys of rats. STH effectively prevented tissue injury, and ameliorated oxidative stress, inflammatory markers, in addition to caspase-3 in CIS-administered rats. STH is rich with antioxidants, suppressed STAT3 protein expression, and upregulated Nrf2 in CIS-administered rats. In conclusion, STH mitigated CIS-induced kidney injury by reducing oxidative stress, suppressing STAT3 and caspase-3, inhibiting pro-inflammatory mediators, and enhancing Nrf2 signaling. On the other hand, metabolomic profiling proposed the presence of 15 metabolites belonging to the chemical classes, phenolic acids, flavonoids and sterols, where phenolic acids were the most abundant classes.https://www.frontiersin.org/articles/10.3389/fphar.2025.1584832/fullcisplatinnephrotoxicitycaspase-3Nrf2oxidative stressSTAT3 cisplatin |
| spellingShingle | Hanan Aati Sultan Y. Aati Hebatallah S. Bahr Asmaa Ramadan Abdel-Sattar Marwa Ahmed Embaby Ahmed M. Reda Ahmed M. Reda Usama Ramadan Abdelmohsen Usama Ramadan Abdelmohsen Gerhard Bringmann Hossam M. Hassan Hossam M. Hassan Mostafa A. Darwish Tamarix honey phenolics attenuate cisplatin-induced kidney toxicity by inhibition of inflammation mediated IL-6/STAT3/TNF-α and oxidative stress-dependent Nrf2/caspase-3 apoptotic signaling pathways Frontiers in Pharmacology cisplatin nephrotoxicity caspase-3 Nrf2 oxidative stress STAT3 cisplatin |
| title | Tamarix honey phenolics attenuate cisplatin-induced kidney toxicity by inhibition of inflammation mediated IL-6/STAT3/TNF-α and oxidative stress-dependent Nrf2/caspase-3 apoptotic signaling pathways |
| title_full | Tamarix honey phenolics attenuate cisplatin-induced kidney toxicity by inhibition of inflammation mediated IL-6/STAT3/TNF-α and oxidative stress-dependent Nrf2/caspase-3 apoptotic signaling pathways |
| title_fullStr | Tamarix honey phenolics attenuate cisplatin-induced kidney toxicity by inhibition of inflammation mediated IL-6/STAT3/TNF-α and oxidative stress-dependent Nrf2/caspase-3 apoptotic signaling pathways |
| title_full_unstemmed | Tamarix honey phenolics attenuate cisplatin-induced kidney toxicity by inhibition of inflammation mediated IL-6/STAT3/TNF-α and oxidative stress-dependent Nrf2/caspase-3 apoptotic signaling pathways |
| title_short | Tamarix honey phenolics attenuate cisplatin-induced kidney toxicity by inhibition of inflammation mediated IL-6/STAT3/TNF-α and oxidative stress-dependent Nrf2/caspase-3 apoptotic signaling pathways |
| title_sort | tamarix honey phenolics attenuate cisplatin induced kidney toxicity by inhibition of inflammation mediated il 6 stat3 tnf α and oxidative stress dependent nrf2 caspase 3 apoptotic signaling pathways |
| topic | cisplatin nephrotoxicity caspase-3 Nrf2 oxidative stress STAT3 cisplatin |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1584832/full |
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