{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:48:20Z","timestamp":1792003700935,"version":"4.4.0"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Life Sciences"],"published-print":{"date-parts":[[2021,6]]},"DOI":"10.1016\/j.lfs.2021.119387","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T03:26:06Z","timestamp":1616556366000},"page":"119387","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":38,"special_numbering":"C","title":["Xanthenone, ACE2 activator, counteracted gentamicin-induced nephrotoxicity in rats: Impact on oxidative stress and ACE2\/Ang-(1\u20137) signaling"],"prefix":"10.1016","volume":"275","author":[{"given":"Maha M.","family":"Abdel-Fattah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel Nasser.A.M.","family":"Elgendy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa R.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.lfs.2021.119387_bb0005","doi-asserted-by":"crossref","first-page":"268","DOI":"10.4062\/biomolther.2012.20.3.268","article-title":"Drug-induced nephrotoxicity and its biomarkers","volume":"20","author":"Kim","year":"2012","journal-title":"Biomol. Ther."},{"key":"10.1016\/j.lfs.2021.119387_bb0010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.lfs.2016.09.014","article-title":"Sinapic acid mitigates gentamicin-induced nephrotoxicity and associated oxidative\/nitrosative stress, apoptosis, and inflammation in rats","volume":"165","author":"Ansari","year":"2016","journal-title":"Life Sci."},{"issue":"6","key":"10.1016\/j.lfs.2021.119387_bb0015","doi-asserted-by":"crossref","first-page":"996","DOI":"10.3109\/0886022X.2016.1165120","article-title":"Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction","volume":"38","author":"Adil","year":"2016","journal-title":"Ren. Fail."},{"issue":"2","key":"10.1016\/j.lfs.2021.119387_bb0020","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1007\/s10157-011-0568-0","article-title":"Involvement of glomerular renin\u2013angiotensin system (RAS) activation in the development and progression of glomerular injury","volume":"16","author":"Kagami","year":"2012","journal-title":"Clin. Exp. Nephrol."},{"issue":"5","key":"10.1016\/j.lfs.2021.119387_bb0025","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1053\/j.ajkd.2015.10.011","article-title":"Renin-angiotensin system inhibitors and kidney and cardiovascular outcomes in patients with CKD: a Bayesian network meta-analysis of randomized clinical trials","volume":"67","author":"Xie","year":"2016","journal-title":"Am. J. Kidney Dis."},{"issue":"3","key":"10.1016\/j.lfs.2021.119387_bb0030","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000269779","article-title":"Nephroprotective effect of telmisartan in rats with ischemia\/reperfusion renal injury","volume":"85","author":"Fouad","year":"2010","journal-title":"Pharmacology"},{"issue":"21","key":"10.1016\/j.lfs.2021.119387_bb0035","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1042\/CS20160343","article-title":"Peroxisome proliferator-activated receptor \u03b1-dependent renoprotection of murine kidney by irbesartan","volume":"130","author":"Harada","year":"2016","journal-title":"Clin. Sci."},{"issue":"11","key":"10.1016\/j.lfs.2021.119387_bb0040","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1080\/10715762.2016.1228923","article-title":"Inhibition of PARP activation by enalapril is crucial for its renoprotective effect in cisplatin-induced nephrotoxicity in rats","volume":"50","author":"Rani","year":"2016","journal-title":"Free Radic. Res."},{"issue":"6","key":"10.1016\/j.lfs.2021.119387_bb0045","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1159\/000262453","article-title":"Protective effects of the angiotensin II receptor blocker losartan on cisplatin-induced kidney injury","volume":"55","author":"Saleh","year":"2009","journal-title":"Chemotherapy"},{"issue":"3\u20134","key":"10.1016\/j.lfs.2021.119387_bb0050","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1159\/000325457","article-title":"Angiotensin II receptor blocker, losartan, ameliorates gentamicin-induced oxidative stress and nephrotoxicity in rats","volume":"87","author":"Heeba","year":"2011","journal-title":"Pharmacology"},{"issue":"9","key":"10.1016\/j.lfs.2021.119387_bb0055","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00210-018-1523-3","article-title":"Modulation of brain ACE and ACE2 may be a promising protective strategy against cerebral ischemia\/reperfusion injury: an experimental trial in rats","volume":"391","author":"Abdel-Fattah","year":"2018","journal-title":"Naunyn Schmiedeberg\u2019s Arch. Pharmacol."},{"issue":"1","key":"10.1016\/j.lfs.2021.119387_bb0060","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/MNH.0000000000000378","article-title":"Angiotensin-converting enzyme 2 and renal disease","volume":"27","author":"Williams","year":"2018","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"issue":"8","key":"10.1016\/j.lfs.2021.119387_bb0065","doi-asserted-by":"crossref","first-page":"F812","DOI":"10.1152\/ajprenal.00655.2013","article-title":"Angiotensin 1\u20137 mediates renoprotection against diabetic nephropathy by reducing oxidative stress, inflammation, and lipotoxicity","volume":"306","author":"Mori","year":"2014","journal-title":"American Journal of Physiology-Renal Physiology"},{"issue":"1","key":"10.1016\/j.lfs.2021.119387_bb0070","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1152\/physrev.00023.2016","article-title":"The ACE2\/angiotensin-(1\u20137)\/MAS axis of the renin-angiotensin system: focus on angiotensin-(1\u20137)","volume":"98","author":"Santos","year":"2018","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.lfs.2021.119387_bb0075","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.peptides.2017.02.001","article-title":"Angiotensin-(1\u20137)-dependent vasorelaxation of the renal artery exhibits unique angiotensin and bradykinin receptor selectivity","volume":"90","author":"Yousif","year":"2017","journal-title":"Peptides"},{"key":"10.1016\/j.lfs.2021.119387_bb0080","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.reprotox.2014.08.006","article-title":"ACE2 activation by xanthenone prevents leptin-induced increases in blood pressure and proteinuria during pregnancy in Sprague-Dawley rats","volume":"49","author":"Ibrahim","year":"2014","journal-title":"Reprod. Toxicol."},{"issue":"6","key":"10.1016\/j.lfs.2021.119387_bb0085","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.tice.2011.09.001","article-title":"Effect of rosmarinic acid on inhibition of gentamicin induced nephrotoxicity in rats","volume":"43","author":"Tavafi","year":"2011","journal-title":"Tissue Cell"},{"issue":"6","key":"10.1016\/j.lfs.2021.119387_bb0090","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1038\/nprot.2006.378","article-title":"Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method","volume":"1","author":"Rahman","year":"2006","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.lfs.2021.119387_bb0095","doi-asserted-by":"crossref","unstructured":"Omar, H.A., Arafa el, S.A., Salama, S.A., Arab, H.H., Wu, C.H., and Weng, J.R., OSU-A9 inhibits angiogenesis in human umbilical vein endothelial cells via disrupting Akt-NF-kappaB and MAPK signaling pathways. Toxicol. Appl. Pharmacol., 2013. 272(3): p. 616\u201324. doi:https:\/\/doi.org\/10.1016\/j.taap.2013.07.014.","DOI":"10.1016\/j.taap.2013.07.014"},{"key":"10.1016\/j.lfs.2021.119387_bb0100","series-title":"Theory and Practice of Histological Techniques","author":"Bancroft","year":"2008"},{"key":"10.1016\/j.lfs.2021.119387_bb0105","series-title":"The Toxicologist\u2019s Pocket Handbook","first-page":"44","author":"Michael","year":"2008"},{"issue":"4","key":"10.1016\/j.lfs.2021.119387_bb0110","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1172\/JCI23378","article-title":"Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system","volume":"115","author":"Crowley","year":"2005","journal-title":"J. Clin. Invest."},{"issue":"7","key":"10.1016\/j.lfs.2021.119387_bb0115","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/emmm.201000080","article-title":"Angiotensin II revisited: new roles in inflammation, immunology and aging","volume":"2","author":"Benigni","year":"2010","journal-title":"EMBO Mol Med"},{"key":"10.1016\/j.lfs.2021.119387_bb0120","doi-asserted-by":"crossref","DOI":"10.1155\/2013\/313528","article-title":"The effects of vitamin D on gentamicin-induced acute kidney injury in experimental rat model","volume":"2013","author":"Hur","year":"2013","journal-title":"Int. J. Endocrinol."},{"issue":"6","key":"10.1016\/j.lfs.2021.119387_bb0125","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1113\/EP086957","article-title":"Neuroprotection by post-stroke administration of an oral formulation of angiotensin-(1-7) in ischaemic stroke","volume":"103","author":"Bennion","year":"2018","journal-title":"Exp. Physiol."},{"issue":"11","key":"10.1016\/j.lfs.2021.119387_bb0130","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1089\/ars.2014.6070","article-title":"Upregulation of angiotensin (1-7)-mediated signaling preserves endothelial function through reducing oxidative stress in diabetes","volume":"23","author":"Zhang","year":"2015","journal-title":"Antioxid. Redox Signal."},{"issue":"9","key":"10.1016\/j.lfs.2021.119387_bb0135","doi-asserted-by":"crossref","first-page":"869","DOI":"10.2174\/0929866524666170728154459","article-title":"Vasodilator effect of angiotensin-(1-7) on vascular coronary bed of rats: role of mas, ACE and ACE2","volume":"24","author":"de Moraes","year":"2017","journal-title":"Protein Pept Lett"},{"issue":"4","key":"10.1016\/j.lfs.2021.119387_bb0140","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s00424-018-2108-1","article-title":"Angiotensin-(1-7)-induced Mas receptor activation attenuates atherosclerosis through a nitric oxide-dependent mechanism in apolipoproteinE-KO mice","volume":"470","author":"Yang","year":"2018","journal-title":"Pflugers Arch."},{"issue":"1","key":"10.1016\/j.lfs.2021.119387_bb0145","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1161\/HYPERTENSIONAHA.117.10280","article-title":"Favorable vascular actions of angiotensin-(1-7) in human obesity","volume":"71","author":"Schinzari","year":"2017","journal-title":"Hypertension"},{"issue":"3","key":"10.1016\/j.lfs.2021.119387_bb0150","doi-asserted-by":"crossref","first-page":"e22254","DOI":"10.1002\/jbt.22254","article-title":"Candesartan and epigallocatechin-3-gallate ameliorate gentamicin-induced renal damage in rats through p38-MAPK and NF-kappaB pathways","volume":"33","author":"Ahmed","year":"2019","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"10.1016\/j.lfs.2021.119387_bb0155","doi-asserted-by":"crossref","unstructured":"Famurewa, A.C., Maduagwuna, E.K., Folawiyo, A.M., Besong, E.E., Eteudo, A.N., Famurewa, O.A., and Ejezie, F.E., Antioxidant, anti-inflammatory, and antiapoptotic effects of virgin coconut oil against antibiotic drug gentamicin-induced nephrotoxicity via the suppression of oxidative stress and modulation of iNOS\/NF-kB\/caspase-3 signaling pathway in Wistar rats. J. Food Biochem., 2019. 44(1): p. e13100.doi:https:\/\/doi.org\/10.1111\/jfbc.13100.","DOI":"10.1111\/jfbc.13100"},{"issue":"4","key":"10.1016\/j.lfs.2021.119387_bb0160","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0305-7372(97)90012-8","article-title":"Free radicals and antioxidants in chemotherapy-induced toxicity","volume":"23","author":"Weijl","year":"1997","journal-title":"Cancer Treat. Rev."},{"key":"10.1016\/j.lfs.2021.119387_bb0165","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.cbi.2016.09.008","article-title":"Tangeretin attenuates cisplatin-induced renal injury in rats: impact on the inflammatory cascade and oxidative perturbations","volume":"258","author":"Arab","year":"2016","journal-title":"Chem. Biol. Interact."},{"issue":"5","key":"10.1016\/j.lfs.2021.119387_bb0170","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1159\/000174085","article-title":"Role of angiotensin II in glomerular injury: lessons from experimental and clinical studies","volume":"19","author":"Hilgers","year":"1996","journal-title":"Kidney Blood Press Res"},{"issue":"10","key":"10.1016\/j.lfs.2021.119387_bb0175","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1681\/ASN.V7102025","article-title":"Angiotensin in progressive renal diseases: theory and practice","volume":"7","author":"Matsusaka","year":"1996","journal-title":"J. Am. Soc. Nephrol."},{"issue":"5","key":"10.1016\/j.lfs.2021.119387_bb0180","doi-asserted-by":"crossref","first-page":"575","DOI":"10.3109\/10715762.2011.560149","article-title":"Telmisartan attenuates oxidative stress and renal fibrosis in streptozotocin induced diabetic mice with the alteration of angiotensin-(1-7) mas receptor expression associated with its PPAR-gamma agonist action","volume":"45","author":"Lakshmanan","year":"2011","journal-title":"Free Radic. Res."},{"issue":"1\u20133","key":"10.1016\/j.lfs.2021.119387_bb0185","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ejphar.2009.01.001","article-title":"Telmisartan, an angiotensin II type 1 receptor blocker, prevents the development of diabetes in male Spontaneously Diabetic Torii rats","volume":"605","author":"Hasegawa","year":"2009","journal-title":"Eur. J. Pharmacol."},{"issue":"4","key":"10.1016\/j.lfs.2021.119387_bb0190","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.bbrc.2005.05.065","article-title":"Increased expression of NAD(P)H oxidase in islets of animal models of type 2 diabetes and its improvement by an AT1 receptor antagonist","volume":"332","author":"Nakayama","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"5","key":"10.1016\/j.lfs.2021.119387_bb0195","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.diabet.2009.04.005","article-title":"Telmisartan attenuates fatty-acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells","volume":"35","author":"Saitoh","year":"2009","journal-title":"Diabetes Metab."},{"issue":"7","key":"10.1016\/j.lfs.2021.119387_bb0200","first-page":"453","article-title":"The protective effect of telmisartan in Type 2 diabetes rat kidneys is related to the downregulation of thioredoxin-interacting protein","volume":"36","author":"Wu","year":"2013","journal-title":"J. Endocrinol. Investig."},{"key":"10.1016\/j.lfs.2021.119387_bb0205","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.lfs.2018.07.021","article-title":"Nephroprotective effect of saxagliptin against gentamicin-induced nephrotoxicity, emphasis on anti-oxidant, anti-inflammatory and anti-apoptic effects","volume":"208","author":"Helal","year":"2018","journal-title":"Life Sci."},{"issue":"2","key":"10.1016\/j.lfs.2021.119387_bb0210","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1080\/15376516.2016.1258748","article-title":"Antioxidant and anti-inflammatory effects of Nasturtium officinale involved in attenuation of gentamicin-induced nephrotoxicity","volume":"27","author":"Shahani","year":"2017","journal-title":"Toxicol. Mech. Methods"},{"key":"10.1016\/j.lfs.2021.119387_bb0215","doi-asserted-by":"crossref","unstructured":"Khajah, M.A., Fateel, M.M., Ananthalakshmi, K.V., and Luqmani, Y.A., Anti-inflammatory action of angiotensin 1-7 in experimental colitis may be mediated through modulation of serum cytokines\/chemokines and immune cell functions. Dev. Comp. Immunol., 2017. 74: p. 200\u2013208. doi:https:\/\/doi.org\/10.1093\/toxsci\/kfj088.","DOI":"10.1016\/j.dci.2017.05.005"},{"issue":"9","key":"10.1016\/j.lfs.2021.119387_bb0220","doi-asserted-by":"crossref","first-page":"5569","DOI":"10.4049\/jimmunol.1000314","article-title":"Anti-inflammatory effects of the activation of the angiotensin-(1-7) receptor, MAS, in experimental models of arthritis","volume":"185","author":"da Silveira","year":"2010","journal-title":"J. Immunol."},{"issue":"4","key":"10.1016\/j.lfs.2021.119387_bb0225","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1053\/j.gastro.2013.06.036","article-title":"Activation of the Mas receptor by angiotensin-(1\u20137) in the renin\u2013angiotensin system mediates mesenteric vasodilatation in cirrhosis","volume":"145","author":"Grace","year":"2013","journal-title":"Gastroenterology"}],"container-title":["Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320521003726?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320521003726?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T15:21:55Z","timestamp":1758986515000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0024320521003726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":45,"alternative-id":["S0024320521003726"],"URL":"https:\/\/doi.org\/10.1016\/j.lfs.2021.119387","relation":{},"ISSN":["0024-3205"],"issn-type":[{"value":"0024-3205","type":"print"}],"subject":[],"published":{"date-parts":[[2021,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Xanthenone, ACE2 activator, counteracted gentamicin-induced nephrotoxicity in rats: Impact on oxidative stress and ACE2\/Ang-(1\u20137) signaling","name":"articletitle","label":"Article Title"},{"value":"Life Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.lfs.2021.119387","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"119387"}}