Systemic toxicity induced by paclitaxel in vivo is associated with the solvent cremophor EL through oxidative stress-driven mechanisms

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorCAMPOS, Fernanda C.
dc.contributor.authorVICTORINO, Vanessa J.
dc.contributor.authorMARTINS-PINGE, Marli Cardoso
dc.contributor.authorCECCHINI, Alessandra L.
dc.contributor.authorPANIS, Carolina
dc.contributor.authorCECCHINI, Rubens
dc.date.accessioned2014-09-30T14:46:36Z
dc.date.available2014-09-30T14:46:36Z
dc.date.issued2014
dc.description.abstractThe toxic effects of paclitaxel (PTX) and its solubilizing agent cremophor EL (CREL) have been well established in vitro; however, the in vivo mechanisms underlying this toxicity remain unclear. Thus, the aim of this study was to analyze the in vivo toxicity induced by infusion of PTX and CREL and to investigate the involvement of oxidative stress as a potential mechanism for this toxicity. We treated male Wistar rats with PTX and/or CREL for 1 h using human-equivalent doses (PTX + CREL/ethanol + NaCl 175 mg/m(2) or CREL + ethanol + NaCl) and sacrificed immediately or 24 h after these drug infusions to systemic biochemical evaluations. Hidrosoluble vitamin E (vitE, Trolox) was added as a control in some groups. The oxidative profile was determined by measuring erythrocyte and plasma lipid peroxidation, superoxide dismutase and catalase activities, reduced glutathione (GSH) levels, red blood cell (RBC) counts, hemoglobin profile, plasma total radical-trapping antioxidant parameter (TRAP), plasma lipid peroxidation, nitric oxide levels and malondialdehyde levels. Our findings showed that CREL infusion triggered immediate high plasma lipid peroxidation and augmented TRAP, while PTX caused immediate TRAP consumption and metahemoglobin formation. Pronounced oxidative effects were detected 24 h after infusion, when CREL treatment enhanced RBC counts and plasma lipid peroxidation, increased catalase activity, and decreased TRAP levels. On the other hand, after 24 h, PTX-infused rats showed reduced catalase activity and reduced metahemoglobin levels. These data indicate the existence of a continuous oxidative stress generation during CREL-PTX treatment and highlight CREL as primarily responsible for the in vivo oxidative damage to RBCs.
dc.description.indexMEDLINE
dc.description.sponsorshipCAPES
dc.description.sponsorshipCNPq
dc.description.sponsorshipFundacaoAraucaria
dc.identifier.citationFOOD AND CHEMICAL TOXICOLOGY, v.68, p.78-86, 2014
dc.identifier.doi10.1016/j.fct.2014.03.013
dc.identifier.eissn1873-6351
dc.identifier.issn0278-6915
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/7758
dc.language.isoeng
dc.publisherPERGAMON-ELSEVIER SCIENCE LTD
dc.relation.ispartofFood and Chemical Toxicology
dc.rightsrestrictedAccess
dc.rights.holderCopyright PERGAMON-ELSEVIER SCIENCE LTD
dc.subjectPaclitaxel
dc.subjectCremophor
dc.subjectOxidative stress
dc.subjectHematological toxicity
dc.subject.otherlipid-peroxidation
dc.subject.othercytotoxicity
dc.subject.otherexpression
dc.subject.otherresistance
dc.subject.otherphenotype
dc.subject.otherchemistry
dc.subject.otherblood
dc.subject.otherassay
dc.titleSystemic toxicity induced by paclitaxel in vivo is associated with the solvent cremophor EL through oxidative stress-driven mechanisms
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalCAMPOS, Fernanda C.:Univ Estadual Londrina, Dept Pathol, Lab Physiopathol & Free Rad, BR-86051990 Londrina, Parana, Brazil
hcfmusp.author.externalMARTINS-PINGE, Marli Cardoso:Univ Estadual Londrina, Dept Physiol Sci, BR-86051990 Londrina, Parana, Brazil
hcfmusp.author.externalCECCHINI, Alessandra L.:Univ Estadual Londrina, Dept Pathol, Lab Physiopathol & Free Rad, BR-86051990 Londrina, Parana, Brazil
hcfmusp.author.externalPANIS, Carolina:Univ Estadual Londrina, Dept Pathol, Lab Physiopathol & Free Rad, BR-86051990 Londrina, Parana, Brazil; State Univ West Parana, UNIOESTE, Francisco Beltrao, Parana, Brazil
hcfmusp.author.externalCECCHINI, Rubens:Univ Estadual Londrina, Dept Pathol, Lab Physiopathol & Free Rad, BR-86051990 Londrina, Parana, Brazil
hcfmusp.citation.scopus47
hcfmusp.contributor.author-fmusphcVANESSA JACOB VICTORINO
hcfmusp.description.beginpage78
hcfmusp.description.endpage86
hcfmusp.description.volume68
hcfmusp.origemWOS
hcfmusp.origem.pubmed24657178
hcfmusp.origem.scopus2-s2.0-84897545161
hcfmusp.origem.wosWOS:000337653000010
hcfmusp.publisher.cityOXFORD
hcfmusp.publisher.countryENGLAND
hcfmusp.relation.referenceAdams J.D., 1993, J NATL CANCER I MONO, V15, P141
hcfmusp.relation.referenceAebi H, 1984, METHOD ENZYMOL, V6, P105, DOI 10.1016/S0076-6879(84)05016-3
hcfmusp.relation.referenceAguirre MV, 2010, EUR J PHARMACOL, V636, P42, DOI 10.1016/j.ejphar.2010.02.056
hcfmusp.relation.referenceAlexandre J, 2007, CANCER RES, V67, P3512, DOI 10.1158/0008-5472.CAN-06-3914
hcfmusp.relation.referenceBiganzoli L, 2009, CRIT REV ONCOL HEMAT, V70, P262, DOI 10.1016/j.critrevonc.2008.07.017
hcfmusp.relation.referenceBrandao HN, 2010, QUIM NOVA, V33, P1359, DOI 10.1590/S0100-40422010000600026
hcfmusp.relation.referenceCosta C.M., 2006, JORNAL BRASILEIRO PA, V5, P345
hcfmusp.relation.referenceFerreira K.A.S.L., 2008, PRATICA HOSP, V57, P143
hcfmusp.relation.referenceFJALLSKOG ML, 1994, EUR J CANCER, V30A, P687, DOI 10.1016/0959-8049(94)90546-0
hcfmusp.relation.referenceFLECHA BG, 1991, FREE RADICAL BIO MED, V10, P93
hcfmusp.relation.referenceGago-Dominguez M, 2007, BREAST CANCER RES, V9, DOI 10.1186/bcr1628
hcfmusp.relation.referenceGay C, 1999, ANAL BIOCHEM, V273, P149, DOI 10.1006/abio.1999.4208
hcfmusp.relation.referenceGelderblom H, 2001, EUR J CANCER, V37, P1590, DOI 10.1016/S0959-8049(01)00171-X
hcfmusp.relation.referenceGutierrez MB, 2006, TOXICOLOGY, V222, P125, DOI 10.1016/j.tox.2006.02.002
hcfmusp.relation.referenceHadzic T, 2010, FREE RADICAL BIO MED, V48, P1024, DOI 10.1016/j.freeradbiomed.2010.01.018
hcfmusp.relation.referenceHalliwell B., 2007, OXYGEN IS TOXIC GAS, P1
hcfmusp.relation.referenceIrizarry L.D., 2009, COMMUNITY ONCOL, V6, P132
hcfmusp.relation.referenceIwase K, 2004, TOXICOL LETT, V154, P143, DOI 10.1016/j.toxlet.2004.08.003
hcfmusp.relation.referenceJemal Ahmedin, 2011, CA Cancer J Clin, V61, P69, DOI 10.3322/caac.20107
hcfmusp.relation.referenceLewis S.M., 2006, HEMATOLOGIA PRATICA
hcfmusp.relation.referenceMark M, 2001, BRIT J PHARMACOL, V134, P1207, DOI 10.1038/sj.bjp.0704387
hcfmusp.relation.referenceMarklund S., 1974, EUR J BIOCHEM, V47, P474
hcfmusp.relation.referenceNavarro-Gonzalvez J.A., 1998, CLIN CHEM, V44, P670
hcfmusp.relation.referenceOliveira F.J.A., 2008, J PARASITOL, V5, P1067
hcfmusp.relation.referencePanis C, 2012, BREAST CANCER RES TR, V133, P89, DOI 10.1007/s10549-011-1693-x
hcfmusp.relation.referenceRamanathan B, 2005, CANCER RES, V65, P8455, DOI 10.1158/0008-5472.CAN-05-1162
hcfmusp.relation.referenceRepetto M, 1996, CLIN CHIM ACTA, V255, P107, DOI 10.1016/0009-8981(96)06394-2
hcfmusp.relation.referenceRocha F.L.R., 2004, REV LATINO AMERICANO, V12, P104
hcfmusp.relation.referenceSamhan-Arias AK, 2011, J CLIN BIOCHEM NUTR, V48, P91, DOI 10.3164/jcbn.11-009FR
hcfmusp.relation.referenceSchechter AN, 2003, NEW ENGL J MED, V348, P1483, DOI 10.1056/NEJMcibr023045
hcfmusp.relation.referenceSchmitz W. O., 2008, Arquivos de Ciências da Saúde da UNIPAR, V12, P175
hcfmusp.relation.referenceSchneider C, 2005, MOL NUTR FOOD RES, V49, P7, DOI 10.1002/mnfr.200400049
hcfmusp.relation.referenceSchneider C. D., 2004, Revista Brasileira de Medicina do Esporte, V10, P308, DOI 10.1590/S1517-86922004000400008
hcfmusp.relation.referenceScripture Charity D, 2005, Ther Clin Risk Manag, V1, P107, DOI 10.2147/tcrm.1.2.107.62910
hcfmusp.relation.referenceSEDLAK J, 1968, ANAL BIOCHEM, V25, P192, DOI 10.1016/0003-2697(68)90092-4
hcfmusp.relation.referenceSouza M.V.N., 2004, QUIM NOVA, V27, P308
hcfmusp.relation.referenceSparreboom A, 1998, CLIN CANCER RES, V4, P1937
hcfmusp.relation.referenceVictorino V.J., 2012, AGE
hcfmusp.relation.referenceWinterbone M.S., 2007, CARDIOVASC DIABETOL, V8, P1
hcfmusp.remissive.sponsorshipCAPES
hcfmusp.remissive.sponsorshipCNPq
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