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

Imagem de Miniatura
Arquivos
art_CAMPOS_Systemic_toxicity_induced_by_paclitaxel_in_vivo_is_2014.PDF (1.33 MB)
Citações na Scopus
47
Tipo de produção
article
Data de publicação
2014
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
PERGAMON-ELSEVIER SCIENCE LTD
Autores
CAMPOS, Fernanda C.
MARTINS-PINGE, Marli Cardoso
CECCHINI, Alessandra L.
PANIS, Carolina
CECCHINI, Rubens
Citação
FOOD AND CHEMICAL TOXICOLOGY, v.68, p.78-86, 2014
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
The 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.
Palavras-chave
Paclitaxel, Cremophor, Oxidative stress, Hematological toxicity
URI
https://observatorio.fm.usp.br/handle/OPI/7758
Referências
  1. Adams J.D., 1993, J NATL CANCER I MONO, V15, P141
  2. Aebi H, 1984, METHOD ENZYMOL, V6, P105, DOI 10.1016/S0076-6879(84)05016-3
  3. Aguirre MV, 2010, EUR J PHARMACOL, V636, P42, DOI 10.1016/j.ejphar.2010.02.056
  4. Alexandre J, 2007, CANCER RES, V67, P3512, DOI 10.1158/0008-5472.CAN-06-3914
  5. Biganzoli L, 2009, CRIT REV ONCOL HEMAT, V70, P262, DOI 10.1016/j.critrevonc.2008.07.017
  6. Brandao HN, 2010, QUIM NOVA, V33, P1359, DOI 10.1590/S0100-40422010000600026
  7. Costa C.M., 2006, JORNAL BRASILEIRO PA, V5, P345
  8. Ferreira K.A.S.L., 2008, PRATICA HOSP, V57, P143
  9. FJALLSKOG ML, 1994, EUR J CANCER, V30A, P687, DOI 10.1016/0959-8049(94)90546-0
  10. FLECHA BG, 1991, FREE RADICAL BIO MED, V10, P93
  11. Gago-Dominguez M, 2007, BREAST CANCER RES, V9, DOI 10.1186/bcr1628
  12. Gay C, 1999, ANAL BIOCHEM, V273, P149, DOI 10.1006/abio.1999.4208
  13. Gelderblom H, 2001, EUR J CANCER, V37, P1590, DOI 10.1016/S0959-8049(01)00171-X
  14. Gutierrez MB, 2006, TOXICOLOGY, V222, P125, DOI 10.1016/j.tox.2006.02.002
  15. Hadzic T, 2010, FREE RADICAL BIO MED, V48, P1024, DOI 10.1016/j.freeradbiomed.2010.01.018
  16. Halliwell B., 2007, OXYGEN IS TOXIC GAS, P1
  17. Irizarry L.D., 2009, COMMUNITY ONCOL, V6, P132
  18. Iwase K, 2004, TOXICOL LETT, V154, P143, DOI 10.1016/j.toxlet.2004.08.003
  19. Jemal Ahmedin, 2011, CA Cancer J Clin, V61, P69, DOI 10.3322/caac.20107
  20. Lewis S.M., 2006, HEMATOLOGIA PRATICA
  21. Mark M, 2001, BRIT J PHARMACOL, V134, P1207, DOI 10.1038/sj.bjp.0704387
  22. Marklund S., 1974, EUR J BIOCHEM, V47, P474
  23. Navarro-Gonzalvez J.A., 1998, CLIN CHEM, V44, P670
  24. Oliveira F.J.A., 2008, J PARASITOL, V5, P1067
  25. Panis C, 2012, BREAST CANCER RES TR, V133, P89, DOI 10.1007/s10549-011-1693-x
  26. Ramanathan B, 2005, CANCER RES, V65, P8455, DOI 10.1158/0008-5472.CAN-05-1162
  27. Repetto M, 1996, CLIN CHIM ACTA, V255, P107, DOI 10.1016/0009-8981(96)06394-2
  28. Rocha F.L.R., 2004, REV LATINO AMERICANO, V12, P104
  29. Samhan-Arias AK, 2011, J CLIN BIOCHEM NUTR, V48, P91, DOI 10.3164/jcbn.11-009FR
  30. Schechter AN, 2003, NEW ENGL J MED, V348, P1483, DOI 10.1056/NEJMcibr023045
  31. Schmitz W. O., 2008, Arquivos de Ciências da Saúde da UNIPAR, V12, P175
  32. Schneider C, 2005, MOL NUTR FOOD RES, V49, P7, DOI 10.1002/mnfr.200400049
  33. Schneider C. D., 2004, Revista Brasileira de Medicina do Esporte, V10, P308, DOI 10.1590/S1517-86922004000400008
  34. Scripture Charity D, 2005, Ther Clin Risk Manag, V1, P107, DOI 10.2147/tcrm.1.2.107.62910
  35. SEDLAK J, 1968, ANAL BIOCHEM, V25, P192, DOI 10.1016/0003-2697(68)90092-4
  36. Souza M.V.N., 2004, QUIM NOVA, V27, P308
  37. Sparreboom A, 1998, CLIN CANCER RES, V4, P1937
  38. Victorino V.J., 2012, AGE
  39. Winterbone M.S., 2007, CARDIOVASC DIABETOL, V8, P1

Coleções
Artigos e Materiais de Revistas Científicas - LIM/51