{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:58:50Z","timestamp":1791773930744,"version":"4.3.4"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2010,9,25]],"date-time":"2010-09-25T00:00:00Z","timestamp":1285372800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2011,4]]},"DOI":"10.1007\/s00204-010-0594-9","type":"journal-article","created":{"date-parts":[[2010,9,24]],"date-time":"2010-09-24T11:17:28Z","timestamp":1285327048000},"page":"347-353","source":"Crossref","is-referenced-by-count":24,"title":["Ticlopidine-induced hepatotoxicity in a GSH-depleted rat model"],"prefix":"10.1007","volume":"85","author":[{"given":"Shinji","family":"Shimizu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Atsumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsunenori","family":"Nakazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Izumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Sudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Okazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Saji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,9,25]]},"reference":[{"key":"594_CR1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/jn\/136.2.373","volume":"136","author":"SR Davis","year":"2006","unstructured":"Davis SR, Quinlivan EP, Stacpoole PW, Gregory JF III (2006) Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women. J Nutr 136:373\u2013378","journal-title":"J Nutr"},{"key":"594_CR2","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1016\/0006-2952(84)90598-7","volume":"33","author":"R Drew","year":"1984","unstructured":"Drew R, Miners JO (1984) The effects of buthionine sulfoximine (BSO) on glutathione depletion and xenobiotic biotransformation. Biochem Pharmacolo 33:2989\u20132994","journal-title":"Biochem Pharmacolo"},{"key":"594_CR3","doi-asserted-by":"crossref","first-page":"7558","DOI":"10.1016\/S0021-9258(18)35980-5","volume":"254","author":"OW Griffith","year":"1979","unstructured":"Griffith OW, Meister A (1979) Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine). J Biol Chem 254:7558\u20137560","journal-title":"J Biol Chem"},{"key":"594_CR4","doi-asserted-by":"crossref","first-page":"12112","DOI":"10.1021\/bi010254c","volume":"40","author":"NT Ha-Duong","year":"2001","unstructured":"Ha-Duong NT, Dijols S, Macherey AC, Goldstein JA, Dansette PM, Mansuy D (2001) Ticlopidine as a selective mechanism-based inhibitor of human cytochrome P450 2C19. Biochemistry 40:12112\u201312122","journal-title":"Biochemistry"},{"key":"594_CR5","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/S0024-3205(00)00722-0","volume":"67","author":"A Hernanz","year":"2000","unstructured":"Hernanz A, Fern\u00e1ndez-Vivancos E, Montiel C, Vazquez JJ, Arnalich F (2000) Changes in the intracellular homocysteine and glutathione content associated with aging. Life Sci 67:1317\u20131324","journal-title":"Life Sci"},{"key":"594_CR6","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/sj.tpj.6500442","volume":"8","author":"K Hirata","year":"2008","unstructured":"Hirata K, Takagi H, Yamamoto M, Matsumoto T, Nishiya T, Mori K, Shimizu S, Masumoto H, Okutani Y (2008) Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case-control study. Pharmacogenomics J 8:29\u201333","journal-title":"Pharmacogenomics J"},{"key":"594_CR7","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1016\/0024-3205(84)90287-X","volume":"34","author":"C Ip","year":"1984","unstructured":"Ip C (1984) Comparative effects of antioxidants on enzymes involved in glutathione metabolism. Life Sci 34:2501\u20132506","journal-title":"Life Sci"},{"key":"594_CR8","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.beha.2004.03.002","volume":"17","author":"AK Jacobson","year":"2004","unstructured":"Jacobson AK (2004) Platelet ADP receptor antagonists: ticlopidine and clopidogrel. Best Pract Res Clin Haematol 17:55\u201364","journal-title":"Best Pract Res Clin Haematol"},{"key":"594_CR9","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1136\/gut.29.9.1153","volume":"2","author":"BH Lauterburg","year":"1988","unstructured":"Lauterburg BH, Velez ME (1988) Glutathione deficiency in alcoholics: risk factor for paracetamol hepatotoxicity. Gut 2:1153\u20131157","journal-title":"Gut"},{"key":"594_CR10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0009-2797(02)00051-0","volume":"142","author":"AP Li","year":"2002","unstructured":"Li AP (2002) A review of the common properties of drugs with idiosyncratic hepatotoxicity and the \u201cmultiple determinant hypothesis\u201d for the manifestation of idiosyncratic drug toxicity. Chem Biol Interact 142:7\u201323","journal-title":"Chem Biol Interact"},{"key":"594_CR11","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1365-2141.1992.tb06412.x","volume":"80","author":"R Mataix","year":"1992","unstructured":"Mataix R, Ojeda E, Perez MC, Jimenez S (1992) Ticlopidine and severe aplastic anaemia. Br J Haematol 80:125\u2013126","journal-title":"Br J Haematol"},{"key":"594_CR12","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s003940200001","volume":"4","author":"P Micke","year":"2002","unstructured":"Micke P, Beeh KM, Buhl R (2002) Effects of long-term supplementation with whey proteins on plasma glutathione levels of HIV-infected patients. Eur J Nutr 4:12\u201318","journal-title":"Eur J Nutr"},{"key":"594_CR13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0022-3565(25)29666-5","volume":"187","author":"JR Mitchell","year":"1973","unstructured":"Mitchell JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB (1973) Acetaminophene-induced hepatic necrosis. IV. Protective role of glutathione. J Pharmacol Exp Ther 187:211\u2013217","journal-title":"J Pharmacol Exp Ther"},{"key":"594_CR14","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.hepres.2005.05.009","volume":"33","author":"M Mizushima","year":"2005","unstructured":"Mizushima M, Iwata N, Fujimoto TT, Ishikawa K, Fujimura K (2005) Patient characteristics in ticlopidine hydrochloride-induced liver injury: Case-control study. Hepatol Res 33:234\u2013240","journal-title":"Hepatol Res"},{"key":"594_CR15","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/0041-008X(87)90094-9","volume":"87","author":"T Mizutani","year":"1987","unstructured":"Mizutani T, Nomura H, Nakanishi K, Fujita S (1987) Hepatotoxicity of butylated hydroxytoluene and its analogs in mice depleted of hepatic glutathione. Toxicol Appl Pharmacol 87:166\u2013176","journal-title":"Toxicol Appl Pharmacol"},{"key":"594_CR16","first-page":"219","volume":"71","author":"T Mizutani","year":"1991","unstructured":"Mizutani T, Satoh K, Nomura H, Nakanishi K (1991) Hepatotoxicity of eugenol in mice depleted of glutathione by treatment with DL-buthionine sulfoximine. Res Commun Chem Pathol Pharmacol 71:219\u2013230","journal-title":"Res Commun Chem Pathol Pharmacol"},{"key":"594_CR17","first-page":"361","volume":"86","author":"T Mizutani","year":"1994","unstructured":"Mizutani T, Irie Y, Nakanishi K (1994a) Styrene-induced hepatotoxicity in mice depleted of glutahione. Res Commun Mol Pathol Pharmacol 86:361\u2013374","journal-title":"Res Commun Mol Pathol Pharmacol"},{"key":"594_CR18","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0300-483X(94)90028-0","volume":"94","author":"T Mizutani","year":"1994","unstructured":"Mizutani T, Nakahori Y, Yamamoto K (1994b) p-Dichlorobenzene-induced hepatotoxicity in mice depleted of glutathione treated with buthionine sulfoximine. Toxicology 94:57\u201367","journal-title":"Toxicology"},{"key":"594_CR19","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/(SICI)1099-1263(199905\/06)19:3<193::AID-JAT553>3.0.CO;2-9","volume":"19","author":"T Mizutani","year":"1999","unstructured":"Mizutani T, Murakami M, Shirai M, Tanaka M, Nakanishi K (1999) Metabolism-dependent hepatotoxicity of Methimazole in mice depleted of glutathione. J Appl Toxicol 19:193\u2013198","journal-title":"J Appl Toxicol"},{"key":"594_CR20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0272-0590(92)90026-E","volume":"19","author":"CA Mugford","year":"1992","unstructured":"Mugford CA, Mortillo M, Mico BA, Tarloff JB (1992) 1-Aminobenzotriazole-induced destruction of hepatic and renal cytochromes P450 in male Sprague-Dawley rats. Fundam Appl Toxicol 19:43\u201349","journal-title":"Fundam Appl Toxicol"},{"key":"594_CR21","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1002\/j.1875-9114.1998.tb03159.x","volume":"18","author":"M Muszkat","year":"1998","unstructured":"Muszkat M, Shapira MY, Sviri S, Linton DM, Caraco Y (1998) Ticlopidine-induced thrombotic thrombocytopenic purpura. Pharmacotherapy 18:1352\u20131355","journal-title":"Pharmacotherapy"},{"key":"594_CR22","doi-asserted-by":"crossref","first-page":"2968","DOI":"10.1161\/01.CIR.0000019739.66514.1E","volume":"105","author":"S Nakamura","year":"2002","unstructured":"Nakamura S, Kugiyama K, Sugiyama S, Miyamoto S, Koide S, Fukushima H, Honda O, Yoshimura M, Ogawa H (2002) Polymorphism in the 5\u2032-flanking region of human glutamate-cysteine ligase modifier subunit gene is associated with myocardial infarction. Circulation 105:2968\u20132973","journal-title":"Circulation"},{"key":"594_CR23","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.taap.2008.06.024","volume":"232","author":"T Nishiya","year":"2008","unstructured":"Nishiya T, Mori K, Hattori C, Kai K, Kataoka H, Masubuchi N, Jindo T, Manabe S (2008) The crucial protective role of glutathione against tienilic acid hepatotoxicity in rats. Toxicol Appl Pharmacol 232:280\u2013291","journal-title":"Toxicol Appl Pharmacol"},{"key":"594_CR24","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1124\/dmd.108.022988","volume":"37","author":"Y Nishiya","year":"2009","unstructured":"Nishiya Y, Hagihara K, Ito T, Tajima M, Miura S, Kurihara A, Farid NA, Ikeda T (2009) Mechanism-based inhibition of human cytochrome P450 2B6 by ticlopidine, clopidogrel, and the thiolactone metabolite of prasugrel. Drug Metab Dispos 37:589\u2013593","journal-title":"Drug Metab Dispos"},{"key":"594_CR25","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/ajh.2830370405","volume":"37","author":"K Ono","year":"1991","unstructured":"Ono K, Kurohara K, Yoshihara M, Shimamoto Y, Yamaguchi M (1991) Agranulocytosis caused by ticlopidine and its mechanism. Am J Hematol 37:239\u2013242","journal-title":"Am J Hematol"},{"issue":"Suppl 1","key":"594_CR26","first-page":"1","volume":"13","author":"E Panak","year":"1983","unstructured":"Panak E, Maffrand JP, Picard-Fraire C, Vall\u00e9e E, Blanchard J, Roncucci R (1983) Ticlopidine: a promise for the prevention and treatment of thrombosis and its complications. Haemostasis 13(Suppl 1):1\u201354","journal-title":"Haemostasis"},{"key":"594_CR27","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.33588\/rn.3311.2001285","volume":"33","author":"AE Pizarro","year":"2001","unstructured":"Pizarro AE, Andrade RJ, Garc\u00eda-Cort\u00e9s M, Lucena MI, P\u00e9rez-Moreno JM, Puertas M, S\u00e1nchez-Mart\u00ednez H, Montero JL, Dur\u00e1n JA, Jim\u00e9nez M, Ruiz-Montero A, Soto-Conesa MJ, Rodrigo L, de Francisco R, Alc\u00e1ntara R, Camargo R (2001) Acute hepatitis due to ticlopidine. A report of 12 cases and review of the literature. Rev Neurol 33:1014\u20131020","journal-title":"Rev Neurol"},{"key":"594_CR28","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1161\/01.CIR.100.15.1667","volume":"100","author":"MJ Quinn","year":"1999","unstructured":"Quinn MJ, Fitzgerald DJ (1999) Ticlopidine and clopidogrel. Circulation 100:1667\u20131672","journal-title":"Circulation"},{"key":"594_CR29","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1124\/jpet.103.056127","volume":"308","author":"T Richter","year":"2004","unstructured":"Richter T, M\u00fcrdter TE, Heinkele G, Pleiss J, Tatzel S, Schwab M, Eichelbaum M, Zanger UM (2004) Potent mechanism-based inhibition of human CYP2B6 by clopidogrel and ticlopidine. J Pharmacol Exp Ther 308:189\u2013197","journal-title":"J Pharmacol Exp Ther"},{"key":"594_CR30","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1021\/tx1000046","volume":"23","author":"Q Ruan","year":"2010","unstructured":"Ruan Q, Zhu M (2010) Investigation of Bioactivation of Ticlopidine Using Linear Ion Trap\/Orbitrap Mass Spectrometry and an Improved Mass Defect Filtering Technique. Chem Res Toxicol 23:909\u2013917","journal-title":"Chem Res Toxicol"},{"key":"594_CR31","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1055\/s-2005-869523","volume":"31","author":"P Savi","year":"2005","unstructured":"Savi P, Herbert JM (2005) Clopidogrel and ticlopidine: P2Y12 adenosine diphosphate-receptor antagonists for the prevention of atherothrombosis. Semin Thromb Hemost 31:174\u2013183","journal-title":"Semin Thromb Hemost"},{"key":"594_CR32","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","volume":"25","author":"J Sedlak","year":"1968","unstructured":"Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman\u2019s reagent. Anal Biochem 25:192\u2013205","journal-title":"Anal Biochem"},{"key":"594_CR33","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s00204-009-0436-9","volume":"83","author":"S Shimizu","year":"2009","unstructured":"Shimizu S, Atsumi R, Itokawa K, Iwasaki M, Aoki T, Ono C, Izumi T, Sudo K, Okazaki O (2009a) Metabolism-dependent hepatotoxicity of amodiaquine in glutathione-depleted mice. Arch Toxicol 83:701\u2013707","journal-title":"Arch Toxicol"},{"key":"594_CR34","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1124\/dmd.109.027524","volume":"37","author":"S Shimizu","year":"2009","unstructured":"Shimizu S, Atsumi R, Nakazawa T, Fujimaki Y, Sudo K, Okazaki O (2009b) Metabolism of ticlopidine in rats: Identification of the main biliary metabolite as a GSH conjugate of S-oxide. Drug Metab Dispos 37:1904\u20131915","journal-title":"Drug Metab Dispos"},{"key":"594_CR35","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/0140-6736(92)90939-Z","volume":"339","author":"FJ Staal","year":"1992","unstructured":"Staal FJ, Ela SW, Roederer M, Anderson MT, Herzenberg LA (1992) Glutathione deficiency and human immunodeficiency virus infection. Lancet 339:909\u2013912","journal-title":"Lancet"},{"key":"594_CR36","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1001\/jama.281.9.806","volume":"281","author":"SR Steinhubl","year":"1999","unstructured":"Steinhubl SR, Tan WA, Foody JM, Topol EJ (1999) Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. EPISTENT Investigators. Evaluation of Platelet IIb\/IIIa Inhibitor for Stenting. JAMA 281:806\u2013810","journal-title":"JAMA"},{"key":"594_CR37","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.hepres.2005.06.009","volume":"33","author":"H Takikawa","year":"2005","unstructured":"Takikawa H (2005) Lessons from ticlopidine-induced liver injury. Hepatol Res 33:193\u2013194","journal-title":"Hepatol Res"},{"key":"594_CR38","first-page":"866","volume":"99","author":"MH Tsai","year":"2000","unstructured":"Tsai MH, Tsai SL, Chen TC, Liaw YF (2000) Ticlopidine-induced cholestatic hepatitis with anti-nuclear antibody in serum. J Formos Med Assoc 99:866\u2013869","journal-title":"J Formos Med Assoc"},{"key":"594_CR39","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1124\/dmd.109.028860","volume":"37","author":"T Usui","year":"2009","unstructured":"Usui T, Mise M, Hashizume T, Yabuki M, Komuro S (2009) Evaluation of the potential for drug-induced liver injury based on in vitro covalent binding to human liver proteins. Drug Metab Dispos 37:2383\u20132392","journal-title":"Drug Metab Dispos"},{"key":"594_CR40","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1155\/1996\/894752","volume":"10","author":"SV Zanten van","year":"1996","unstructured":"van Zanten SV, McCormic CW (1996) Antinuclear antibody-positive ticlopidine-induced hepatitis. Can J Gastroenterol 10:231\u2013232","journal-title":"Can J Gastroenterol"},{"key":"594_CR41","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2131\/jts.28.455","volume":"28","author":"T Watanabe","year":"2003","unstructured":"Watanabe T, Sagisaka H, Arakawa S, Shibaya Y, Watanabe M, Igarashi I, Tanaka K, Totsuka S, Takasaki W, Manabe S (2003) A novel model of continuous depletion of glutathione in mice treated with l-buthionine (S, R)-sulfoximine. J Toxicol Science 28:455\u2013463","journal-title":"J Toxicol Science"},{"key":"594_CR42","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/sj.bjp.0705808","volume":"142","author":"K Yoneda","year":"2004","unstructured":"Yoneda K, Iwamura R, Kishi H, Mizukami Y, Mogami K, Kobayashi S (2004) Identification of the active metabolite of ticlopidine from rat in vitro metabolites. Br J Pharmacol 142:551\u2013557","journal-title":"Br J Pharmacol"},{"key":"594_CR43","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/03602530902843483","volume":"41","author":"SF Zhou","year":"2009","unstructured":"Zhou SF, Liu JP, Chowbay B (2009) Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev 41:89\u2013295","journal-title":"Drug Metab Rev"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-010-0594-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00204-010-0594-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-010-0594-9","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T01:28:58Z","timestamp":1740533338000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00204-010-0594-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,25]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2011,4]]}},"alternative-id":["594"],"URL":"https:\/\/doi.org\/10.1007\/s00204-010-0594-9","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,25]]}}}