start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Ethyl acetate extract of Ceiba pentandra (L.) Gaertn. reduces methotrexate-induced renal damage in rats via antioxidant, anti-inflammatory, and antiapoptotic actions en-subtitle= kn-subtitle= en-abstract= kn-abstract= Methotrexate (MTX) is a chemotherapeutic agent and an immunosuppressant used to treat cancer and autoimmune diseases. However, its use is limited by its multi-organ toxicity, including nephrotoxicity, which is related to MTX-driven oxidative stress. Silencing oxidative stressors is therefore an important strategy in minimizing MTX adverse effects.Medicinal plants rich in phenolic compounds are probable candidates to overcome these oxidants. Herein, C. pentandra ethyl acetate extract showed powerful in vitro radical-scavenging potential (IC50 = 0.0716) comparable to those of the standard natural (ascorbic acid, IC50 = 0.045) and synthetic (BHA, IC50 = 0.056) antioxidants. The effect of C. pentandra ethyl acetate extract against MTX-induced nephrotoxicity in rats was evaluated by administering the extract (400 mg/kg/day) or the standard antioxidant silymarin (100 mg/kg/day) orally for 5 days before and 5 days after a single MTX injection (20 mg/kg, i.p.).C. pentandra showed slight superiorities over silymarin in restoring the MTX-impaired renal functions, with approximately twofold decreases in overall kidney function tests. C. pentandra also improved renal antioxidant capacity and reduced the MTX-induced oxidative stress. Moreover, C. pentandra inhibited MTX-initiated apoptotic and inflammatory cascades, and attenuated MTX-induced histopathological changes in renal tissue architecture.Phytochemical investigation of the extract led to the purification of the phenolics quercitrin (1), cinchonains 1a (2) and 1b (3), cis-clovamide (4), trans-clovamide (5), and glochidioboside (6); a structurally similar with many of the reported antioxidant and nephroprotective agents. In conclusion, these data demonstrate that C. pentandra exhibits nephroprotective effect against MTX-induced kidney damage via its antioxidant, antiapoptotic and anti-inflammatory mechanisms. TaxonomyFunctional Disorder, Traditional Medicine, Herbal Medicine. en-copyright= kn-copyright= en-aut-name=Abouelela Mohamed E. en-aut-sei=Abouelela en-aut-mei= Mohamed E. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=Orabi Mohamed A.A. en-aut-sei=Orabi en-aut-mei= Mohamed A.A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Abdelhamid Reda A. en-aut-sei=Abdelhamid en-aut-mei= Reda A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Abdelkader Mohamed S. en-aut-sei=Abdelkader en-aut-mei= Mohamed S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Madkor Hafez R. en-aut-sei=Madkor en-aut-mei= Hafez R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Darwish Faten M.M. en-aut-sei=Darwish en-aut-mei= Faten M.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=Hatano Tsutomu en-aut-sei=Hatano en-aut-mei= Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=Elsadek Bakheet E.M. en-aut-sei=Elsadek en-aut-mei= Bakheet E.M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University kn-affil= affil-num=2 en-affil=Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University kn-affil= affil-num=3 en-affil=Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University kn-affil= affil-num=4 en-affil=Department of Pharmacognosy, Faculty of Pharmacy, Sohag University kn-affil= affil-num=5 en-affil=Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University kn-affil= affil-num=6 en-affil=Department of Pharmacognosy, Faculty of Pharmacy, Assiut University kn-affil= affil-num=7 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University kn-affil= en-keyword=Ceiba pentandra(L.) Gaertn. kn-keyword=Ceiba pentandra(L.) Gaertn. en-keyword=Methotrexate kn-keyword=Methotrexate en-keyword=Nephrotoxicity kn-keyword=Nephrotoxicity en-keyword=Antioxidant kn-keyword=Antioxidant END