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Many previous pieces of literature proved the marked cardio and neurotoxicity of the drug. Thus, this research provides evidence on the alleviative effect of flavocoxid on the cardiac and brain toxicity of cyclophosphamide in mice and determines its underlying mechanisms. Flavocoxid (Flavo) is a potent antioxidant and anti-inflammatory agent that inhibits the peroxidase activity of cyclooxygenase (COX-1 and COX-2) enzymes and 5-lipooxygenase (\n                    <jats:italic>5-LOX<\/jats:italic>\n                    ). Flavo was administered orally (20\u00a0mg\/kg) for 2\u00a0weeks, followed by Cyclo (100\u00a0mg\/kg, i.p.) on day 14. Higher heart and brain weight indices, serum lactate dehydrogenase (LDH), creatine kinase (CK-MB), and nitric oxide (NO) were mitigated following Flavo administration. Flavo modulated oxidative stress biomarkers (malonaldehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD)), tumor necrosis factor-\u03b1 (TNF\n                    <jats:italic>-<\/jats:italic>\n                    \u03b1), and interleukin (IL)-1\u03b2. Additionally, cardiac troponin I (cTn-I), nuclear factor kappa B (NF-\u03baB), brain amyloid precursor protein (APP), and granulocyte macrophage colony-stimulating factor (GM-CSF) were decreased by Flavo administration. Moreover, Flavo ameliorated heart and brain histopathological changes and caspase-3 levels. Collectively, Flavo (20\u00a0mg\/kg) for 14\u00a0days showed significant cardio and neuroprotective effects due to its antioxidant, anti-inflammatory, and antiapoptotic activities via modulation of oxidative stress, inflammation, and the GM-CSF\/NF-\u03baB signaling pathway.\n                  <\/jats:p>","DOI":"10.1007\/s11356-022-20441-5","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T03:13:22Z","timestamp":1652670802000},"page":"69635-69651","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Ameliorative effect of flavocoxid on cyclophosphamide-induced cardio and neurotoxicity via targeting the GM-CSF\/NF-\u03baB signaling pathway"],"prefix":"10.1007","volume":"29","author":[{"given":"Fatma F.","family":"Elsayed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waad M.","family":"Elshenawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman M.","family":"Khalifa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed R.","family":"Rizq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania R.","family":"Abdelaziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"20441_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cbi.2018.07.001","volume":"292","author":"RR Abdelaziz","year":"2018","unstructured":"Abdelaziz RR, Elmahdy M, Suddek GM (2018) Flavocoxid attenuates airway inflammation in ovalbumin-induced mouse asthma model. 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