{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:43:36Z","timestamp":1791085416224,"version":"4.1.0"},"reference-count":61,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Food and Chemical Toxicology"],"published-print":{"date-parts":[[2008,7]]},"DOI":"10.1016\/j.fct.2008.03.033","type":"journal-article","created":{"date-parts":[[2008,4,8]],"date-time":"2008-04-08T11:18:56Z","timestamp":1207653536000},"page":"2422-2428","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":127,"title":["Silymarin prevents adriamycin-induced cardiotoxicity and nephrotoxicity in rats"],"prefix":"10.1016","volume":"46","author":[{"given":"Nagla A.","family":"El-Shitany","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"El-Haggar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karema","family":"El-desoky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.fct.2008.03.033_bib1","series-title":"Clinical Chemistry","first-page":"1112","article-title":"Creatinine kinase","author":"Abbot","year":"1984"},{"issue":"6","key":"10.1016\/j.fct.2008.03.033_bib2","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S1043661802002311","article-title":"Alpha-lipoic acid ameliorates myocardial toxicity induced by doxorubicin","volume":"46","author":"Al-majed","year":"2002","journal-title":"Pharmacol. Res."},{"issue":"4","key":"10.1016\/j.fct.2008.03.033_bib3","first-page":"291","article-title":"Abatement by naringenin of doxorubicin-induced cardiac toxicity in rats","volume":"17","author":"Arafa","year":"2005","journal-title":"J. Egypt. Nat. Cancer Inst."},{"key":"10.1016\/j.fct.2008.03.033_bib4","first-page":"193","article-title":"Serum creatinine determination without protein precipitation","volume":"37","author":"Bartles","year":"1972","journal-title":"Clin. Chem. Acta"},{"key":"10.1016\/j.fct.2008.03.033_bib5","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/ki.1986.212","article-title":"Tubulo-interstitial lesions mediate renal damage in adriamycin glomerulopathy","volume":"30","author":"Bertani","year":"1986","journal-title":"Kidney Int."},{"key":"10.1016\/j.fct.2008.03.033_bib6","first-page":"865","article-title":"Anthracycline cardiomyopathy monitored by morphologic changes","volume":"62","author":"Billingham","year":"1978","journal-title":"Cancer Treat. Rep."},{"key":"10.1016\/j.fct.2008.03.033_bib7","doi-asserted-by":"crossref","first-page":"249","DOI":"10.7326\/0003-4819-80-2-249","article-title":"Adriamycin. A new anticancer drug with significant clinical activity","volume":"80","author":"Blum","year":"1974","journal-title":"Ann. Intern. Med."},{"key":"10.1016\/j.fct.2008.03.033_bib8","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0162-0134(01)00198-2","article-title":"Silybin, a new iron-chelating agent","volume":"85","author":"Borsari","year":"2001","journal-title":"J. Inorg. Biochem."},{"issue":"7","key":"10.1016\/j.fct.2008.03.033_bib9","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1248\/bpb.28.1165","article-title":"Antioxidative and cardioprotective effects of Phyllanthus urinaria L. on doxorubicin-induced cardiotoxicity","volume":"28","author":"Chularojmontri","year":"2005","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.fct.2008.03.033_bib10","doi-asserted-by":"crossref","first-page":"3060","DOI":"10.1016\/S0021-9258(17)35746-0","article-title":"Redox cycling of anthracyclines by cardiac mitochondria: anthracycline radical formation by NADPH dehydrogenous","volume":"261","author":"Davies","year":"1986","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.fct.2008.03.033_bib11","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1472-8206.1998.tb00951.x","article-title":"Tissue injury by reactive oxygen species and the protective effects of flavonoids","volume":"12","author":"De Groot","year":"1998","journal-title":"Fundam. Clin. Pharmacol."},{"key":"10.1016\/j.fct.2008.03.033_bib12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/ndt\/16.1.147","article-title":"Altered antioxidant defence in a mouse adriamycin model of glomerulosclerosis","volume":"16","author":"Deman","year":"2001","journal-title":"Nephrol. Dial. Transpl."},{"key":"10.1016\/j.fct.2008.03.033_bib13","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1016\/S0021-9258(17)35747-2","article-title":"Redox cycling of anthracyclines by cardiac mitochondria. II. Formation of superoxide anion, hydrogen peroxide, and hydroxyl radical","volume":"261","author":"Doroshow","year":"1986","journal-title":"J. Biol. Chem."},{"issue":"4","key":"10.1016\/j.fct.2008.03.033_bib14","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1016\/S0959-8049(96)00314-0","article-title":"Cardioprotection of rat heart myocytes with amifostine (ethyol) and its free thiol, WR-1065, in vitro","volume":"32","author":"Dorr","year":"1996","journal-title":"Eur. J. Cancer"},{"key":"10.1016\/j.fct.2008.03.033_bib15","first-page":"214","article-title":"Tissue sulfhydryl groups","volume":"74","author":"Ellman","year":"1959","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.fct.2008.03.033_bib16","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/jat.945","article-title":"Protective effect of caffeic acid phenethyl ester on doxorubicin-induced cardiotoxicity in rats","volume":"24","author":"Fadillioglu","year":"2004","journal-title":"J. Appl. Toxicol."},{"key":"10.1016\/j.fct.2008.03.033_bib17","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1136\/jcp.13.2.156","article-title":"A rapid and precise method for the determination of urea","volume":"13","author":"Fawcett","year":"1960","journal-title":"J. Clin. Pathol."},{"key":"10.1016\/j.fct.2008.03.033_bib18","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0304-4157(84)90013-3","article-title":"Anthracycline glycoside-membrane interactions","volume":"779","author":"Goormaghtigh","year":"1984","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.fct.2008.03.033_bib19","series-title":"Clinical Chemistry: Principles and Techniques","first-page":"819","article-title":"Colorimetric determination of lactic dehydrogenase","author":"Henry","year":"1974"},{"key":"10.1016\/j.fct.2008.03.033_bib20","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s002800050048","article-title":"Comparison of the protective effects of amifostine and dexrazoxane against the toxicity of doxorubicin in spontaneously hypertensive rats","volume":"45","author":"Herman","year":"2000","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.fct.2008.03.033_bib21","first-page":"39","article-title":"Natural products for liver disease","volume":"2","author":"Hikino","year":"1988","journal-title":"Econ. Med. Plant. Res."},{"issue":"2","key":"10.1016\/j.fct.2008.03.033_bib22","first-page":"727","article-title":"Lipid lowering: an important factor in preventing adriamycin induced heart failure","volume":"150","author":"Iliskovic","year":"1997","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.fct.2008.03.033_bib23","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1620\/tjem.204.85","article-title":"Successful allogeneic bone marrow transplantation for acute myelogenous leukemia after drug-induced cardiomyopathy","volume":"204","author":"Itoh","year":"2004","journal-title":"Tohoku J. Exp. Med."},{"issue":"8","key":"10.1016\/j.fct.2008.03.033_bib24","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1515\/CCLM.2005.140","article-title":"Counteracting adriamycin-induced oxidative stress by administration of N-acetyl cysteine and vitamin E","volume":"43","author":"Kalaiselvi","year":"2005","journal-title":"Clin. Chem. Lab. Med."},{"issue":"21","key":"10.1016\/j.fct.2008.03.033_bib25","first-page":"12610","article-title":"Suppression of doxorubicin cardiotoxicity by overexpression of catalase in the heart of transgenic mice","volume":"271","author":"Kang","year":"1996","journal-title":"Am. Soc. Biochem. Mol. Biol."},{"issue":"3","key":"10.1016\/j.fct.2008.03.033_bib26","first-page":"383","article-title":"Cisplatin nephrotoxicity and protection by milk thistle extract in rats","volume":"2","author":"Karimi","year":"2005","journal-title":"Adv. Access. Pub. eCAM"},{"key":"10.1016\/j.fct.2008.03.033_bib27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/clinchem\/18.3.199","article-title":"Estimation of total lipids in serum and tissues","volume":"18","author":"Knight","year":"1972","journal-title":"Clin. Chem."},{"key":"10.1016\/j.fct.2008.03.033_bib28","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/S0022-3565(25)39493-0","article-title":"Inhibitory effect of 5,6,7,8-tetrahydroneoterin on adriamycin induced cardiotoxicity","volume":"266","author":"Koima","year":"1993","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"1","key":"10.1016\/j.fct.2008.03.033_bib29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.5507\/bp.2005.002","article-title":"Silybin and silymarin \u2013 new effects and applications","volume":"149","author":"Kren","year":"2005","journal-title":"Biomed. Papers"},{"key":"10.1016\/j.fct.2008.03.033_bib30","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1254\/jjp.39.323","article-title":"Hyperlipidemic effects of adriamycin in rats","volume":"39","author":"Kunitomo","year":"1985","journal-title":"Jpn. J. Pharmacol."},{"key":"10.1016\/j.fct.2008.03.033_bib31","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1152\/ajpheart.01023.2001","article-title":"Melatonin as an effective protector against doxorubicin-induced cardiotoxicity","volume":"283","author":"Liu","year":"2002","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"10.1016\/j.fct.2008.03.033_bib32","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1023\/A:1024175325850","article-title":"The influence of lipoic acid on adriamycin-induced hyperlipidemic nephrotoxicity in rats","volume":"247","author":"Malarkodi","year":"2003","journal-title":"Mol. Cell. Biochem."},{"issue":"6","key":"10.1016\/j.fct.2008.03.033_bib33","first-page":"656","article-title":"Silymarin modulates cisplatin-induced oxidative stress and hepatotoxicity in rats","volume":"39","author":"Mansour","year":"2006","journal-title":"J. Biochem. Mol. Biol."},{"key":"10.1016\/j.fct.2008.03.033_bib34","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1006\/phrs.1998.0432","article-title":"Effect of captopril on doxorubicin-induced nephrotoxicity in normal rats","volume":"39","author":"Mansour","year":"1999","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.fct.2008.03.033_bib35","first-page":"427","article-title":"Amelioration of glomerular injury in doxorubicin hydrochloride nephrosis by diethylthiourea","volume":"118","author":"Milner","year":"1991","journal-title":"J. Lab. Clin. Med."},{"key":"10.1016\/j.fct.2008.03.033_bib36","doi-asserted-by":"crossref","first-page":"4327","DOI":"10.1016\/0006-2952(86)90713-6","article-title":"A possible role of membrane lipid peroxidation in anthracycline nephrotoxicity","volume":"35","author":"Mimnaugh","year":"1986","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.fct.2008.03.033_bib37","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1211\/0022357023565","article-title":"Protection against doxorubicin cardiomyopathy in rats: role of phosphodiesterase inhibitors type 4","volume":"56","author":"Mohamed","year":"2004","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.fct.2008.03.033_bib38","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S1071-9164(99)90010-6","article-title":"A canine model of heart failure by intracoronary adriamycin injection: Hemodynamic and energetic results","volume":"5","author":"Monnet","year":"1999","journal-title":"J. Card. Fail."},{"key":"10.1016\/j.fct.2008.03.033_bib39","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/BF03189986","article-title":"Comparative bioavailability of silipide, a new flavanolignan complex, in rats","volume":"17","author":"Morazzoni","year":"1992","journal-title":"Eur. J. Drug. Metab. Pharmacokinet."},{"key":"10.1016\/j.fct.2008.03.033_bib40","first-page":"16","article-title":"Protection against acute adriamycin-induced cardiotoxicity by garlic: role of endogenous antioxidants and inhibition of TNF-\u03b1 expression. BMC","volume":"3","author":"Mukherjee","year":"2003","journal-title":"Pharmacology"},{"key":"10.1016\/j.fct.2008.03.033_bib41","first-page":"863","article-title":"Effects of silymarin (Legalon) therapy on the antioxidant defense mechanism and lipid peroxidation in alcoholic liver disease","volume":"131","author":"Muzes","year":"1990","journal-title":"Orv. Hetil."},{"issue":"3","key":"10.1016\/j.fct.2008.03.033_bib42","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1006\/phrs.1999.0585","article-title":"Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible Mechanism of protection","volume":"41","author":"Nagi","year":"2000","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.fct.2008.03.033_bib43","first-page":"62","article-title":"Adriamycin-induced chronic protenuria: a structural and function study","volume":"106","author":"O\u2019Donnell","year":"1985","journal-title":"J. Lab. Clin. Med."},{"key":"10.1016\/j.fct.2008.03.033_bib44","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1006\/phrs.2002.0990","article-title":"Radioprotective effect of silymarin against radiation induced hepatotoxicity","volume":"45","author":"Ramadan","year":"2002","journal-title":"Pharmacol. Res."},{"issue":"12","key":"10.1016\/j.fct.2008.03.033_bib45","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1093\/clinchem\/19.12.1350","article-title":"Preparation and properties of a cholesterol oxidase from Nocardia sp and its application to the enzymatic assay of total cholesterol in serum","volume":"19","author":"Richmond","year":"1973","journal-title":"Clin. Chem."},{"key":"10.1016\/j.fct.2008.03.033_bib46","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1006\/phrs.2000.0769","article-title":"The prevention role of deferoxamine against acute doxorubicin-induced cardiac, renal and hepatic toxicity in rats","volume":"43","author":"Saad","year":"2001","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.fct.2008.03.033_bib47","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1074\/jbc.274.5.2750","article-title":"Enhanced glutathione levels and oxidoresistance mediated by increased glucose-6-phosphate dehydrogenase expression","volume":"274","author":"Salvemini","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.fct.2008.03.033_bib48","doi-asserted-by":"crossref","first-page":"47","DOI":"10.7326\/0003-4819-125-1-199607010-00008","article-title":"Anthracycline-induced cardiotoxicity","volume":"125","author":"Shan","year":"1996","journal-title":"Ann. Intern. Med."},{"key":"10.1016\/j.fct.2008.03.033_bib49","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0022-2828(87)80392-9","article-title":"Subcellular effects of adriamycin in the heart: a concise review","volume":"19","author":"Singal","year":"1987","journal-title":"J. Mol. Cell. Cardiol."},{"issue":"1","key":"10.1016\/j.fct.2008.03.033_bib50","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1161\/01.CIR.91.1.10","article-title":"Probucol protects against adriamycin cardiomyopathy without interfering with antitumor effect","volume":"91","author":"Siveski-lliskovic","year":"1995","journal-title":"Circulation"},{"key":"10.1016\/j.fct.2008.03.033_bib51","first-page":"87","article-title":"Effect of silymarin on serum cholesterol levels in rats","volume":"141","author":"Skottova","year":"1998","journal-title":"Acta. Univ. Palacki. Olomuc. Fac. Med."},{"issue":"4","key":"10.1016\/j.fct.2008.03.033_bib52","doi-asserted-by":"crossref","first-page":"324","DOI":"10.3177\/jnsv.53.324","article-title":"Taurine prevents oxidative damage of high glucose-induced cataractogenesis in isolated rat lenses","volume":"53","author":"Son","year":"2007","journal-title":"J. Nutr. Sci. Vitaminol. (Tokyo)"},{"key":"10.1016\/j.fct.2008.03.033_bib53","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/S0022-3565(25)38707-0","article-title":"Effect of vitamin A administration on resistance of rat heart against doxorubicin-induced cardiotoxicity and lethality","volume":"269","author":"Tesoriere","year":"1994","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.fct.2008.03.033_bib54","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0003-2697(78)90342-1","article-title":"Determination of malondialdehyde precursor in tissues by thiobarbituric acid test","volume":"86","author":"Uchiyama","year":"1979","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.fct.2008.03.033_bib55","first-page":"13","article-title":"Cardiac disease induced by chronic adriamycin administration in dogs and an evaluation of vitamin E and selenium as cardioprotectants","volume":"99","author":"Van Vleet","year":"1980","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.fct.2008.03.033_bib56","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1111\/j.2042-7158.1996.tb06007.x","article-title":"Protective effect of butylatedhydroxyanisol on adriamycin-induced cardiotoxicity","volume":"48","author":"Vora","year":"1996","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.fct.2008.03.033_bib57","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1159\/000188398","article-title":"\u03b1-Tocopherol improves focal glomerulosclerosis in rats with adriamycin-induced progressive renal failure","volume":"68","author":"Washio","year":"1994","journal-title":"Nephron"},{"issue":"2","key":"10.1016\/j.fct.2008.03.033_bib58","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0022-3565(24)37822-X","article-title":"Inhibition of buthionine sulfoximine-enhanced doxorubicin toxicity in metallothionein overexpressing transgenic mouse heart","volume":"287","author":"Wu","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"8","key":"10.1016\/j.fct.2008.03.033_bib59","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0024-3205(00)00990-5","article-title":"Effects by doxorubicin on the myocardium are mediated by oxygen free radicals","volume":"68","author":"Xu","year":"2001","journal-title":"Life. Sci."},{"key":"10.1016\/j.fct.2008.03.033_bib60","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S1043-6618(03)00185-3","article-title":"Erdosteine prevents doxorubicin-induced cardiotoxicity in rats","volume":"48","author":"Yagmurca","year":"2003","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.fct.2008.03.033_bib61","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.tox.2005.10.015","article-title":"Protective effect of lycopene on adriamycin-induced cardiotoxicity and nephrotoxicity","volume":"218","author":"Yilmaz","year":"2006","journal-title":"Toxicology"}],"container-title":["Food and Chemical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691508001579?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691508001579?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T20:42:42Z","timestamp":1759524162000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0278691508001579"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7]]},"references-count":61,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2008,7]]}},"alternative-id":["S0278691508001579"],"URL":"https:\/\/doi.org\/10.1016\/j.fct.2008.03.033","relation":{},"ISSN":["0278-6915"],"issn-type":[{"value":"0278-6915","type":"print"}],"subject":[],"published":{"date-parts":[[2008,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Silymarin prevents adriamycin-induced cardiotoxicity and nephrotoxicity in rats","name":"articletitle","label":"Article Title"},{"value":"Food and Chemical Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fct.2008.03.033","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2008 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}