{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:36:08Z","timestamp":1790876168726,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T00:00:00Z","timestamp":1564963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cyclophosphamide (CP) is a widely used chemotherapeutic agent; however, its clinical application is limited because of its multi-organ toxicity. Galangin (Gal) is a bioactive flavonoid with promising biological activities. This study investigated the hepatoprotective effect of Gal in CP-induced rats. Rats received Gal (15, 30 and 60 mg\/kg\/day) for 15 days followed by a single dose of CP at day 16. Cyclophosphamide triggered liver injury characterized by elevated serum transaminases, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and histopathological manifestations. Increased hepatic reactive oxygen species, malondialdehyde, nitric oxide, and oxidative DNA damage along with declined glutathione and antioxidant enzymes were demonstrated in CP-administered rats. CP provoked hepatic nuclear factor-kappaB (NF-\u03baB) phosphorylation and increased mRNA abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-\u03b1) and interleukin-1 beta (IL-1\u03b2) both expression and serum levels. Gal prevented CP-induced liver injury, boosted antioxidants and suppressed oxidative stress, DNA damage, NF-\u03baB phosphorylation and pro-inflammatory mediators. Gal diminished Bax and caspase-3, and increased B-cell lymphoma-2 (Bcl-2) in liver of CP-administered rats. In addition, Gal increased peroxisome proliferator-activated receptor gamma (PPAR\u03b3) expression and activated hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) signaling showed by the increase in Nrf2, NAD(P)H: quinone acceptor oxidoreductase-1 (NQO-1) and heme oxygenase 1 (HO-1) in CP-administered rats. These findings suggest that Gal prevents CP hepatotoxicity through activation of Nrf2\/HO-1 signaling and attenuation of oxidative damage, inflammation and cell death. Therefore, Gal might represent a promising adjuvant therapy to prevent hepatotoxicity in patients on CP treatment.<\/jats:p>","DOI":"10.3390\/biom9080346","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T11:17:47Z","timestamp":1565003867000},"page":"346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":206,"title":["Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity"],"prefix":"10.3390","volume":"9","author":[{"given":"Saleem H.","family":"Aladaileh","sequence":"first","affiliation":[{"name":"Department of Medical Analysis, Princess Aisha Bint Al-Hussein Faculty of Nursing and Health Sciences, Al-Hussein Bin Talal University, Ma\u2019an 71111, Jordan"},{"name":"Department of Biology, Faculty of Science, Al-Hussein Bin Talal University, Ma\u2019an 71111, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4018-6925","authenticated-orcid":false,"given":"Mohammad H.","family":"Abukhalil","sequence":"additional","affiliation":[{"name":"Department of Medical Analysis, Princess Aisha Bint Al-Hussein Faculty of Nursing and Health Sciences, Al-Hussein Bin Talal University, Ma\u2019an 71111, Jordan"},{"name":"Department of Biology, Faculty of Science, Al-Hussein Bin Talal University, Ma\u2019an 71111, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7134-3199","authenticated-orcid":false,"given":"Sultan A. M.","family":"Saghir","sequence":"additional","affiliation":[{"name":"Department of Medical Analysis, Princess Aisha Bint Al-Hussein Faculty of Nursing and Health Sciences, Al-Hussein Bin Talal University, Ma\u2019an 71111, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9230-3858","authenticated-orcid":false,"given":"Hamza","family":"Hanieh","sequence":"additional","affiliation":[{"name":"Department of Medical Analysis, Princess Aisha Bint Al-Hussein Faculty of Nursing and Health Sciences, Al-Hussein Bin Talal University, Ma\u2019an 71111, Jordan"},{"name":"Department of Biology, Faculty of Science, Al-Hussein Bin Talal University, Ma\u2019an 71111, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal A.","family":"Alfwuaires","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer A.","family":"Almaiman","sequence":"additional","affiliation":[{"name":"Department of Applied Medical Sciences, Community College of Unaizah, Qassim University, Buraydah 51431, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3017-9924","authenticated-orcid":false,"given":"May","family":"Bin-Jumah","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 84428, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0279-6500","authenticated-orcid":false,"given":"Ayman M.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.biopha.2016.12.047","article-title":"Possible involvement of nrf2 and ppar\u03b3 up-regulation in the protective effect of umbelliferone against cyclophosphamide-induced hepatotoxicity","volume":"86","author":"Mahmoud","year":"2017","journal-title":"Biomed. 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