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ACR-induced acute kidney injury is mediated through several signals. In this research, we investigated, for the first time, the therapeutic effects of phytochemicals apocynin (APO) and\/or umbelliferone (UMB) against ACR-induced nephrotoxicity in rats and emphasized the underlying molecular mechanism. To achieve this goal, five groups of rats were randomly assigned: the control group received vehicle (0.5% CMC; 1 ml\/rat), ACR (40 mg\/kg, i.p.), ACR\u2009+\u2009APO (100 mg\/kg, P.O.), ACR\u2009+\u2009UMB (50 mg\/kg, P.O.), and combination group for 10 days. In ACR-intoxicated rats, there was a significant reduction in weight gain while the levels of blood urea, uric acid, creatinine, and Kim-1 were elevated, indicating renal injury. Histopathological injury was also observed in the kidneys of ACR-intoxicated rats, confirming the biochemical data. Moreover, MDA, TNF-\u03b1, and IL-1\u03b2 levels were raised; and GSH and SOD levels were decreased. In contrast, treatment with APO, UMB, and their combination significantly reduced the kidney function biomarkers, prevented tissue damage, and decreased inflammatory cytokines and MDA. Mechanistically, it suppressed the expression of NLRP-3, ASC, GSDMD, caspase-1, and IL-1\u03b2, while it upregulated Nrf-2 and HO-1 in the kidneys of ACR-intoxicated rats. In conclusion, APO, UMB, and their combination prevented ACR-induced nephrotoxicity in rats by attenuating oxidative injury and inflammation, suppressing NLRP-3 inflammasome signaling, enhancing antioxidants, and upregulating Nrf-2 and HO-1 in the kidneys of ACR-induced rats.<\/jats:p>","DOI":"10.1007\/s00210-024-03271-9","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T10:01:37Z","timestamp":1721383297000},"page":"569-580","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Renoprotective effects of apocynin and\/or umbelliferone against acrylamide-induced acute kidney injury in rats: role of the NLRP3 inflammasome and Nrf-2\/HO-1 signaling pathways"],"prefix":"10.1007","volume":"398","author":[{"given":"Saad A.","family":"Ageena","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel G.","family":"Bakr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamada A.","family":"Mokhlis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed F.","family":"Abd-Ellah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"issue":"8","key":"3271_CR1","doi-asserted-by":"publisher","first-page":"4499","DOI":"10.1002\/ptr.7153","volume":"35","author":"OAM Abd El-Ghafar","year":"2021","unstructured":"Abd El-Ghafar OAM, Hassanein EHM, Sayed AM, Rashwan EK, Shalkami AS, Mahmoud AM (2021) Acetovanillone prevents cyclophosphamide-induced acute lung injury by modulating PI3K\/Akt\/mTOR and Nrf2 signaling in rats. 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