{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:47:54Z","timestamp":1789508874774,"version":"build-2803163510"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T00:00:00Z","timestamp":1556064000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2019,5]]},"DOI":"10.1007\/s00204-019-02429-2","type":"journal-article","created":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T09:04:49Z","timestamp":1556096689000},"page":"1417-1431","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Involvement of Nrf2\/HO-1 antioxidant signaling and NF-\u03baB inflammatory response in the potential protective effects of vincamine against methotrexate-induced nephrotoxicity in rats: cross talk between nephrotoxicity and neurotoxicity"],"prefix":"10.1007","volume":"93","author":[{"given":"Youssef M.","family":"Shalaby","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther T.","family":"Menze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0253-8280","authenticated-orcid":false,"given":"Samar S.","family":"Azab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza S.","family":"Awad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,24]]},"reference":[{"key":"2429_CR1","doi-asserted-by":"publisher","first-page":"1516","DOI":"10.1080\/0886022X.2016.1216722","volume":"38","author":"SM Abd El-Twab","year":"2016","unstructured":"Abd El-Twab SM, Hozayen WG, Hussein OE, Mahmoud AM (2016) 18 \u03b2-glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2\/ARE\/HO-1 pathway and endogenous antioxidants. Ren Fail 38:1516\u20131527","journal-title":"Ren Fail"},{"key":"2429_CR2","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.taap.2018.07.014","volume":"356","author":"AE Abdel-Maged","year":"2018","unstructured":"Abdel-Maged AE, Gad AM, Abdel-Aziz AK, Aboulwafa MM, Azab SS (2018) Comparative study of anti-VEGF ranibizumab and interleukin-6 receptor antagonist tocilizumab in adjuvant-induced arthritis. Toxicol Appl Pharmacol 356:65\u201375","journal-title":"Toxicol Appl Pharmacol"},{"key":"2429_CR3","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s00210-013-0949-x","volume":"387","author":"IT Abdel-Raheem","year":"2014","unstructured":"Abdel-Raheem IT, Khedr NF (2014) Renoprotective effects of montelukast, a cysteinyl leukotriene receptor antagonist, against methotrexate-induced kidney damage in rats. Naunyn-Schmiedeberg\u2019s Arch Pharmacol 387:341\u2013353","journal-title":"Naunyn-Schmiedeberg\u2019s Arch Pharmacol"},{"key":"2429_CR4","first-page":"1","volume":"25","author":"OM Abdel-Salam","year":"2015","unstructured":"Abdel-Salam OM, Hamdy SM, Seadawy SAM, Galal AF, Abouelfadl DM, Atrees SS (2015) Effect of piracetam, vincamine, vinpocetine, and donepezil on oxidative stress and neurodegeneration induced by aluminum chloride in rats. Comp Clin Pathol 25:1\u201314","journal-title":"Comp Clin Pathol"},{"key":"2429_CR5","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s00580-015-2182-0","volume":"25","author":"OM Abdel-Salam","year":"2016","unstructured":"Abdel-Salam OM, Hamdy SM, Seadawy SAM, Galal AF, Abouelfadl DM, Atrees SS (2016) Effect of piracetam, vincamine, vinpocetine, and donepezil on oxidative stress and neurodegeneration induced by aluminum chloride in rats. Comp Clin Pathol 25:305\u2013318","journal-title":"Comp Clin Pathol"},{"key":"2429_CR6","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1200\/JCO.1987.5.12.2017","volume":"5","author":"SP Ackland","year":"1987","unstructured":"Ackland SP, Schilsky RL (1987) High-dose methotrexate: a critical reappraisal. J Clin Oncol 5:2017\u20132031","journal-title":"J Clin Oncol"},{"key":"2429_CR7","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","volume":"105","author":"H Aebi","year":"1984","unstructured":"Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121\u2013126","journal-title":"Methods Enzymol"},{"key":"2429_CR8","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1080\/01480545.2017.1289221","volume":"41","author":"A Al Maruf","year":"2018","unstructured":"Al Maruf A, O\u2019Brien PJ, Naserzadeh P, Fathian R, Salimi A, Pourahmad J (2018) Methotrexate induced mitochondrial injury and cytochrome c release in rat liver hepatocytes. Drug Chem Toxicol 41:51\u201361","journal-title":"Drug Chem Toxicol"},{"key":"2429_CR9","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1136\/ard.54.9.708","volume":"54","author":"GS Alarcon","year":"1995","unstructured":"Alarcon GS, Tracy IC, Strand GM, Singh K, Macaluso M (1995) Survival and drug discontinuation analyses in a large cohort of methotrexate treated rheumatoid arthritis patients. Ann Rheum Dis 54:708","journal-title":"Ann Rheum Dis"},{"key":"2429_CR10","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.bcp.2018.09.004","volume":"156","author":"AE Ali","year":"2018","unstructured":"Ali AE, Mahdy HM, Elsherbiny DM, Azab SS (2018) Rifampicin ameliorates lithium-pilocarpine-induced seizures, consequent hippocampal damage and memory deficit in rats: impact on oxidative, inflammatory and apoptotic machineries. Biochem Pharmacol 156:431\u2013443. \n                    https:\/\/doi.org\/10.1016\/j.bcp.2018.09.004","journal-title":"Biochem Pharmacol"},{"key":"2429_CR11","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1016\/j.jfda.2017.05.001","volume":"25","author":"H Asci","year":"2017","unstructured":"Asci H, Ozmen O, Ellidag HY, Aydin B, Bas E, Yilmaz N (2017) The impact of gallic acid on the methotrexate-induced kidney damage in rats. J Food Drug Anal 25:890\u2013897","journal-title":"J Food Drug Anal"},{"key":"2429_CR12","first-page":"1003","volume":"15","author":"I Asvadi","year":"2011","unstructured":"Asvadi I, Hajipour B, Asvadi A, Asl N, Roshangar L, Khodadadi A (2011) Protective effect of pentoxyfilline in renal toxicity after methotrexate administration. Eur Rev Med Pharmacol Sci 15:1003\u20131009","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2429_CR13","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.lfs.2005.09.012","volume":"78","author":"MJ Balunas","year":"2005","unstructured":"Balunas MJ, Kinghorn AD (2005) Drug discovery from medicinal plants. Life Sci 78:431\u2013441","journal-title":"Life Sci"},{"key":"2429_CR14","volume-title":"Theory and practice of histological technique","author":"J Banchroft","year":"1996","unstructured":"Banchroft J, Stevens A, Turner D (1996) Theory and practice of histological technique, 4th edn. Churchill Livingstone, New York","edition":"4th"},{"key":"2429_CR15","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1111\/1523-1747.ep12506462","volume":"78","author":"PP Bradley","year":"1982","unstructured":"Bradley PP, Priebat DA, Christensen RD, Rothstein G (1982) Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Investig Dermatol 78:206\u2013209","journal-title":"J Investig Dermatol"},{"key":"2429_CR16","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1681\/ASN.2012050536","volume":"24","author":"J-M Bugnicourt","year":"2013","unstructured":"Bugnicourt J-M, Godefroy O, Chillon J-M, Choukroun G, Massy ZA (2013) Cognitive disorders and dementia in CKD: the neglected kidney\u2013brain axis. J Am Soc Nephrol 24:353\u2013363","journal-title":"J Am Soc Nephrol"},{"key":"2429_CR17","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1136\/jnnp.65.6.810","volume":"65","author":"D Burn","year":"1998","unstructured":"Burn D, Bates D (1998) Neurology and the kidney. J Neurol Neurosurg Psychiatry 65:810\u2013821","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2429_CR18","doi-asserted-by":"publisher","first-page":"734","DOI":"10.3109\/0886022X.2015.1012984","volume":"37","author":"DO Dabak","year":"2015","unstructured":"Dabak DO, Kocaman N (2015) Effects of silymarin on methotrexate-induced nephrotoxicity in rats. Ren Fail 37:734\u2013739","journal-title":"Ren Fail"},{"key":"2429_CR19","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1111\/j.1523-1755.2004.00354.x","volume":"65","author":"T Deguchi","year":"2004","unstructured":"Deguchi T, Kusuhara H, Takadate A, Endou H, Otagiri M, Sugiyama Y (2004) Characterization of uremic toxin transport by organic anion transporters in the kidney. Kidney Int 65:162\u2013174","journal-title":"Kidney Int"},{"key":"2429_CR20","doi-asserted-by":"publisher","first-page":"5727","DOI":"10.1007\/s12035-017-0797-7","volume":"55","author":"SE El-Agamy","year":"2018","unstructured":"El-Agamy SE, Abdel-Aziz AK, Wahdan S, Esmat A, Azab SS (2018) Astaxanthin ameliorates doxorubicin-induced cognitive impairment (chemobrain) in experimental rat model: impact on oxidative, inflammatory, and apoptotic machineries. Mol Neurobiol 55:5727\u20135740. \n                    https:\/\/doi.org\/10.1007\/s12035-017-0797-7","journal-title":"Mol Neurobiol"},{"key":"2429_CR21","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.lfs.2018.04.002","volume":"202","author":"AM El-Dessouki","year":"2018","unstructured":"El-Dessouki AM, El Fattah MA, Awad AS, Zaki HF (2018) Zafirlukast and vincamine ameliorate tamoxifen-induced oxidative stress and inflammation: Role of the JNK\/ERK pathway. Life Sci 202:78\u201388","journal-title":"Life Sci"},{"issue":"4","key":"2429_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/859383","volume":"2015","author":"AA El-Sheikh","year":"2015","unstructured":"El-Sheikh AA, Morsy MA, Abdalla AM, Hamouda AH, Alhaider IA (2015) Mechanisms of thymoquinone hepatorenal protection in methotrexate-induced toxicity in rats. Mediators Inflamm 2015(4):1\u201312","journal-title":"Mediators Inflamm"},{"key":"2429_CR23","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/s00280-015-2924-3","volume":"77","author":"TE Fandy","year":"2016","unstructured":"Fandy TE, Abdallah I, Khayat M, Colby DA, Hassan HE (2016) In vitro characterization of transport and metabolism of the alkaloids: vincamine, vinpocetine and eburnamonine. Cancer Chemother Pharmacol 77:259\u2013267","journal-title":"Cancer Chemother Pharmacol"},{"key":"2429_CR24","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1136\/jcp.13.2.156","volume":"13","author":"J Fawcett","year":"1960","unstructured":"Fawcett J, Scott J (1960) A rapid and precise method for the determination of urea. J Clin Pathol 13:156\u2013159","journal-title":"J Clin Pathol"},{"key":"2429_CR25","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1007\/s12011-009-8550-3","volume":"136","author":"A-HA Fayed","year":"2010","unstructured":"Fayed A-HA (2010) Brain trace element concentration of rats treated with the plant alkaloid, vincamine. Biol Trace Elem Res 136:314\u2013319","journal-title":"Biol Trace Elem Res"},{"key":"2429_CR26","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/0002-9343(80)90105-9","volume":"68","author":"E Frei","year":"1980","unstructured":"Frei E et al (1980) High dose methotrexate with leucovorin rescue: rationale and spectrum of antitumor activity. Am J Med 68:370\u2013376","journal-title":"Am J Med"},{"key":"2429_CR27","doi-asserted-by":"crossref","first-page":"A.3F.1","DOI":"10.1002\/0471140856.txa03fs32","volume":"32","author":"SR Gallagher","year":"2007","unstructured":"Gallagher SR (2007) One\u2010dimensional SDS gel electrophoresis of proteins. Curr Protoc Toxicol 32:A.3F.1\u2013A.3F.38","journal-title":"Curr Protoc Toxicol"},{"key":"2429_CR28","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.eplepsyres.2016.06.010","volume":"126","author":"S Ghafouri","year":"2016","unstructured":"Ghafouri S, Fathollahi Y, Javan M, Shojaei A, Asgari A, Mirnajafi-Zadeh J (2016) Effect of low frequency stimulation on impaired spontaneous alternation behavior of kindled rats in Y-maze test. Epilepsy Res 126:37\u201344","journal-title":"Epilepsy Res"},{"key":"2429_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejphar.2015.08.047","volume":"768","author":"HM Hafez","year":"2015","unstructured":"Hafez HM, Ibrahim MA, Ibrahim SA, Amin EF, Goma W, Abdelrahman AM (2015) Potential protective effect of etanercept and aminoguanidine in methotrexate-induced hepatotoxicity and nephrotoxicity in rats. Eur J Pharmacol 768:1\u201312","journal-title":"Eur J Pharmacol"},{"key":"2429_CR30","doi-asserted-by":"publisher","first-page":"123","DOI":"10.4103\/0973-1296.196309","volume":"13","author":"J Han","year":"2017","unstructured":"Han J, Qu Q, Qiao J, Zhang J (2017) Vincamine alleviates amyloid-\u03b2 25\u201335 peptides-induced cytotoxicity in PC12 cells. Pharmacogn Mag 13:123","journal-title":"Pharmacogn Mag"},{"key":"2429_CR31","first-page":"525","volume-title":"Principles and techniques. Clinical Chemistry","author":"R Henry","year":"1974","unstructured":"Henry R, Cannon D, Winkelman J (1974) Principles and techniques. Clinical Chemistry, 2nd edn. Harper and Row, New York, p 525","edition":"2"},{"key":"2429_CR32","doi-asserted-by":"publisher","first-page":"420","DOI":"10.2144\/01312rr04","volume":"31","author":"S Karamohamed","year":"2001","unstructured":"Karamohamed S, Guidotti G (2001) Bioluminometric method for real-time detection of ATPase activity. Biotechniques 31:420\u2013425","journal-title":"Biotechniques"},{"issue":"2","key":"2429_CR33","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.semnephrol.2005.09.003","volume":"26","author":"KJ Kelly","year":"2006","unstructured":"Kelly KJ (2006) Acute renal failure: much more than a kidney disease. Semin Nephrol\u00a026(2):105\u2013113","journal-title":"Semin Nephrol"},{"key":"2429_CR34","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/nrneurol.2009.138","volume":"5","author":"AV Krishnan","year":"2009","unstructured":"Krishnan AV, Kiernan MC (2009) Neurological complications of chronic kidney disease. Nat Rev Neurol 5:542","journal-title":"Nat Rev Neurol"},{"key":"2429_CR35","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1159\/000369817","volume":"128","author":"B Lisowska-Myjak","year":"2014","unstructured":"Lisowska-Myjak B (2014) Uremic toxins and their effects on multiple organ systems. Nephron Clin Pract 128:303\u2013311","journal-title":"Nephron Clin Pract"},{"key":"2429_CR36","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1681\/ASN.2007080901","volume":"19","author":"M Liu","year":"2008","unstructured":"Liu M et al (2008) Acute kidney injury leads to inflammation and functional changes in the brain. J Am Soc Nephrol 19:1360\u20131370","journal-title":"J Am Soc Nephrol"},{"key":"2429_CR37","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1097\/FPC.0b013e32835c3b24","volume":"23","author":"E Lopez-Lopez","year":"2013","unstructured":"Lopez-Lopez E et al (2013) Polymorphisms in the methotrexate transport pathway: a new tool for MTX plasma level prediction in pediatric acute lymphoblastic leukemia. Pharmacogenet Genom 23:53\u201361","journal-title":"Pharmacogenet Genom"},{"key":"2429_CR38","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/315641a0","volume":"315","author":"CJ March","year":"1985","unstructured":"March CJ et al (1985) Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature 315:641","journal-title":"Nature"},{"key":"2429_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/387071","volume":"2013","author":"MA Morsy","year":"2013","unstructured":"Morsy MA, Ibrahim SA, Amin EF, Kamel MY, Rifaai RA, Hassan MK (2013) Curcumin ameliorates methotrexate-induced nephrotoxicity in rats. Adv Pharmacol Sci 2013:1\u20137","journal-title":"Adv Pharmacol Sci"},{"key":"2429_CR40","doi-asserted-by":"publisher","first-page":"66226","DOI":"10.18632\/oncotarget.19887","volume":"8","author":"N Muhammad","year":"2017","unstructured":"Muhammad N, Steele R, Isbell TS, Philips N, Ray RB (2017) Bitter melon extract inhibits breast cancer growth in preclinical model by inducing autophagic cell death. Oncotarget 8:66226","journal-title":"Oncotarget"},{"key":"2429_CR41","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.1016\/j.jnutbio.2013.07.005","volume":"24","author":"S Mukherjee","year":"2013","unstructured":"Mukherjee S et al (2013) Pomegranate reverses methotrexate-induced oxidative stress and apoptosis in hepatocytes by modulating Nrf2-NF-\u03baB pathways. J Nutr Biochem 24:2040\u20132050","journal-title":"J Nutr Biochem"},{"key":"2429_CR42","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.2215\/CJN.02440314","volume":"10","author":"SK Nigam","year":"2015","unstructured":"Nigam SK, Wu W, Bush KT, Hoenig MP, Blantz RC, Bhatnagar V (2015) Handling of drugs, metabolites, and uremic toxins by kidney proximal tubule drug transporters. Clin J Am Soc Nephrol 10:2039\u20132049","journal-title":"Clin J Am Soc Nephrol"},{"key":"2429_CR43","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/S0006-291X(72)80218-3","volume":"46","author":"M Nishikimi","year":"1972","unstructured":"Nishikimi M, Rao NA, Yagi K (1972) The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun 46:849\u2013854","journal-title":"Biochem Biophys Res Commun"},{"key":"2429_CR44","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","volume":"95","author":"H Ohkawa","year":"1979","unstructured":"Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351\u2013358","journal-title":"Anal Biochem"},{"key":"2429_CR45","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1191\/0748233706th265oa","volume":"22","author":"F \u00d6ktem","year":"2006","unstructured":"\u00d6ktem F, Yilmaz HR, Ozguner F, Olgar S, Ayata A, Uzar E, Uz E (2006) Methotrexate-induced renal oxidative stress in rats: the role of a novel antioxidant caffeic acid phenethyl ester. Toxicol Ind Health 22:241\u2013247","journal-title":"Toxicol Ind Health"},{"key":"2429_CR46","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/bs.acc.2014.11.007","volume":"68","author":"A Onopiuk","year":"2015","unstructured":"Onopiuk A, Tokarzewicz A, Gorodkiewicz E (2015) Cystatin C: a kidney function biomarker. Adv Clin Chem\u00a068:57\u201369","journal-title":"Adv Clin Chem"},{"key":"2429_CR47","doi-asserted-by":"publisher","first-page":"925","DOI":"10.3109\/0886022X.2014.900599","volume":"36","author":"A Otunctemur","year":"2014","unstructured":"Otunctemur A et al (2014) Protective effect of hydrogen sulfide on gentamicin-induced renal injury. Ren Fail 36:925\u2013931","journal-title":"Ren Fail"},{"key":"2429_CR48","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1146\/annurev-immunol-031210-101312","volume":"29","author":"W Ouyang","year":"2011","unstructured":"Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG (2011) Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 29:71\u2013109","journal-title":"Annu Rev Immunol"},{"key":"2429_CR49","doi-asserted-by":"publisher","first-page":"475","DOI":"10.18433\/J3M89Q","volume":"17","author":"T Sato","year":"2014","unstructured":"Sato T, Yamaguchi H, Kogawa T, Abe T, Mano N (2014) Organic anion transporting polypeptides 1B1 and 1B3 play an important role in uremic toxin handling and drug-uremic toxin interactions in the liver. J Pharm Pharm Sci 17:475\u2013484","journal-title":"J Pharm Pharm Sci"},{"key":"2429_CR50","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1002\/biof.1041","volume":"39","author":"S Shishodia","year":"2013","unstructured":"Shishodia S (2013) Molecular mechanisms of curcumin action: gene expression. Biofactors 39:37\u201355","journal-title":"Biofactors"},{"key":"2429_CR51","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1104\/pp.010999","volume":"128","author":"BS Tiwari","year":"2002","unstructured":"Tiwari BS, Belenghi B, Levine A (2002) Oxidative stress increased respiration and generation of reactive oxygen species, resulting in ATP depletion, opening of mitochondrial permeability transition, and programmed cell death. Plant Physiol 128:1271\u20131281","journal-title":"Plant Physiol"},{"key":"2429_CR52","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s11095-007-9407-0","volume":"25","author":"AL VanWert","year":"2008","unstructured":"VanWert AL, Sweet DH (2008) Impaired clearance of methotrexate in organic anion transporter 3 (Slc22a8) knockout mice: a gender specific impact of reduced folates. Pharm Res 25:453\u2013462","journal-title":"Pharm Res"},{"key":"2429_CR53","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1007\/s13105-012-0219-2","volume":"69","author":"N Vardi","year":"2013","unstructured":"Vardi N, Parlakpinar H, Ates B, Cetin A, Otlu A (2013) The protective effects of Prunus armeniaca L (apricot) against methotrexate-induced oxidative damage and apoptosis in rat kidney. J Physiol Biochem 69:371\u2013381","journal-title":"J Physiol Biochem"},{"key":"2429_CR54","first-page":"45","volume":"44","author":"A Vassault","year":"1986","unstructured":"Vassault A et al (1986) Protocole de validation de techniques. Ann Biol Clin 44:45","journal-title":"Ann Biol Clin"},{"key":"2429_CR55","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/S0887-2333(00)00036-9","volume":"14","author":"T Walker","year":"2000","unstructured":"Walker T, Rhodes P, Westmoreland C (2000) The differential cytotoxicity of methotrexate in rat hepatocyte monolayer and spheroid cultures. Toxicol In Vitro 14:475\u2013485","journal-title":"Toxicol In Vitro"},{"key":"2429_CR56","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1634\/theoncologist.11-6-694","volume":"11","author":"BC Widemann","year":"2006","unstructured":"Widemann BC, Adamson PC (2006) Understanding and managing methotrexate nephrotoxicity. Oncologist 11:694\u2013703","journal-title":"Oncologist"},{"key":"2429_CR57","doi-asserted-by":"publisher","first-page":"5865","DOI":"10.1016\/j.bmcl.2013.08.095","volume":"23","author":"JR Woods","year":"2013","unstructured":"Woods JR, Riofski MV, Zheng MM, O\u2019Banion MA, Mo H, Kirshner J, Colby DA. Bioorganic (2013) Synthesis of 15-methylene-eburnamonine from (+)-vincamine, evaluation of anticancer activity, and investigation of mechanism of action by quantitative NMR. Bioorg Med Chem Lett 23:5865\u20135869","journal-title":"Bioorg Med Chem Lett"},{"key":"2429_CR58","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1177\/0960327116637414","volume":"36","author":"Y Yuksel","year":"2016","unstructured":"Yuksel Y, Yuksel R, Yagmurca M, Haltas H, Erdamar H, Toktas M, Ozcan O (2016) Effects of quercetin on methotrexate-induced nephrotoxicity in rats. Human Exp Toxicol 36:51\u201361","journal-title":"Human Exp Toxicol"},{"key":"2429_CR59","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1139\/cjpp-2013-0097","volume":"91","author":"HF Zaki","year":"2013","unstructured":"Zaki HF, Abdelsalam RM (2013) Vinpocetine protects liver against ischemia\u2013reperfusion injury. Can J Physiol Pharmacol 91:1064\u20131070","journal-title":"Can J Physiol Pharmacol"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-019-02429-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00204-019-02429-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-019-02429-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T23:06:32Z","timestamp":1587596792000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00204-019-02429-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,24]]},"references-count":59,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["2429"],"URL":"https:\/\/doi.org\/10.1007\/s00204-019-02429-2","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,24]]},"assertion":[{"value":"21 December 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}