• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Master's Dissertation
DOI
10.11606/D.9.2009.tde-15012010-130114
Document
Author
Full name
Fernanda Júdice Pinedo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Farsky, Sandra Helena Poliselli (President)
Hebeda, Cristina Bichels
Moreau, Regina Lucia de Moraes
Title in Portuguese
Efeitos da hidroquinona sobre atividades funcionais da célula endotelial e de neutrófilos
Keywords in Portuguese
Célula endotelial
Enzimas de biotransformação
Hidroquinona
Mediadores inflamatórios
Moléculas de adesão
Neutrófilos
Abstract in Portuguese
A hidroquinona (HQ) é um composto fenólico obtido a partir da metabolização endógena do benzeno, está presente no cigarro, medicamentos, reveladores fotográficos, alimentos e plantas medicinais. Temos demonstrado que a intoxicação experimental de ratos à HQ compromete a migração de leucócitos para o pulmão na vigência de resposta inflamatória alérgica ou inespecífica. O presente trabalho visou avaliar os efeitos da HQ sobre atividades da célula endotelial e de neutrófilos envolvidas na inflamação. Culturas primárias de células endoteliais da rede microcirculatória obtidas do músculo cremaster de ratos Wistar, machos, foram tratadas com HQ (10 ou 100 µM, 2 horas) e posteriormente incubadas ou não com LPS de E. coli (LPS; 2 µg/mL). Neutrófilos obtidos da cavidade peritoneal de ratos Wistar, 4 horas após a injeção local de glicogênio de ostra (10 mL, 1%) , foram tratados com HQ (5 ou 10 µM, 1 hora) e, em seguida, foram incubados ou não com LPS (5 µg/mL). Células controles receberam volumes equivalentes dos veículos da HQ e do LPS. Os dados obtidos mostram que o tratamento com a HQ não induziu necrose ou apoptose em ambos os tipos celulares; reduziu a produção de NO pela célula endotelial e por neutrófilos, por bloqueio das atividades das óxido nítrico sintases; reduziu a expressão gênica e protéica de TNF-α, IL-6 e IL-1β induzida pelo LPS em neutrófilos, possivelmente decorrente de redução da translocação nuclear do NFκB; por outro lado aumentou a expressão gênica e protéica basal de TNF-α, IL-1β, ICAM-1, PECAM-1 e VCAM-1, bem como a translocação nuclear do NF-κB; reduziu a atividade fagocítica e microbicida de neutrófilos frente a Candida albicans; não afetou a expressão gênica da CYP2E1 em ambos os tipos celulares, mas aumentou a expressão gênica de MPO em neutrófilos. Em conjunto, os dados permitem concluir que a HQ atua diferentemente nos dois tipos de células estudadas, ativando e inibindo propriedades inflamatórias na célula endotelial e nos neutrófilos, respectivamente. É possível as ações sobre os neutrófilos possam contribuir, pelo menos em parte, pela redução da migração celular durante a resposta inflamatória observada após exposição in vivo à HQ.
Title in English
Effect of hydroquinone in the functional activity of endothelial cells and neutrophils
Keywords in English
Adhesion molecules
Biotransformation enzymes
Endothelial cells
Hydroquinone
Inflammatory mediators
Neutrophil
Abstract in English
Hydroquinone (HQ) is a fenolic compound obtained after benzene metabolism, it is a component of cigarette, medicines, photographic developer, and it is also finding in some foods and medicinal herbs. Our research group has been shown that rats in vivo exposed to HQ present impaired leukocyte migration into lung during allergic or non-specific inflammation. In the present study, we investigate the effects of HQ on functional activities of neutrophils and endothelial cells (EC) involved in inflammation. Primary cultured EC was obtained from microcirculatory network of male Wistar rats, and treated with HQ (10 or 100 µM, two hours). After the treatments, EC was incubated in presence or absence of lipopolissacharide of E. coli (LPS; 2 µg/mL). Peritoneal neutrophils obtained four hours after local injection of oyster glycogen (10 mL, 1%) were incubated with HQ (5 or 10 µM, one hour) and in sequence it was incubated in presence or absence of LPS (5 µg/mL) .Control cells were cultured with equivalent volumes of HQ and LPS vehicle. Results obtained showed that treatment with HQ did not induce apoptosis or necrosis in both types of cells; impaired NO production by endothelial cells and neutrophils dependent on blockade of Ca+2-dependent and independent NOS activity; decreased gene and protein expression of TNF-α, IL-6 and IL-1β in neutrophils induced by LPS, possibly due to reduced nuclear translocation of the NF-κB. On the other hand, HQ treatment enhanced basal protein and gene expression of TNF-α, IL-1β , ICAM-1, PECAM-1 and VCAM-1 and the nuclear translocation of NF-κB; impaired Candida albicans phagocytic and killing indexes; did not affect the gene expression of CYP2E1 in both types of cell, but increased the gene expression of MPO in neutrophils. Taken together, results obtained show that HQ acts differently in the two types of cells studied, activating and inhibiting inflammatory properties in endothelial cells and neutrophils, respectively. Actions on neutrophils may contribute, at least in part, on the reduced leukocyte recruitment during in vivo HQ exposure.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Versao_Final_usp.pdf (2.46 Mbytes)
Publishing Date
2010-04-16
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
Centro de Informática de São Carlos
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2020. All rights reserved.