RESUMO
The in vitro photoinactivation of human tumor cell lines and sheep red blood cells (SRBC) by Zinc (II) Phthalocyanine (ZnPc) was investigated using unilamellar liposome (LUV) as delivery system, in the presence and absence of cholesterol (CHOL) in the formulation. The presence of CHOL improves the stability of the system showing to be essential for the photodynamic action of ZnPc. LUVs prepared without CHOL did not present any antiproliferative effects neither induced significant photohaemolysis. The presence of ZnPc in the culture medium caused total cell growth inhibition (TGI) only at concentrations higher than 250 micromol dm(-3). For ZnPc in LUV/CHOL (mass ratio=3:1), the mean TGI values for almost all studied cells were around 80 micromol dm(-3), and 14 micromol dm(-3) for human ovarian carcinoma (NIH: OVCAR-3) cells. The cytoplasmic components of OVCAR-3 and SRBC when irradiated in presence of ZnPc in LUV/CHOL were completely destroyed, culminating in cell swelling, lysis and death by necrosis.
Assuntos
Colesterol/química , Eritrócitos/efeitos da radiação , Indóis/química , Lipossomos/química , Compostos Organometálicos/química , Radiossensibilizantes/química , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Indóis/uso terapêutico , Isoindóis , Microscopia Eletrônica de Transmissão , Compostos Organometálicos/uso terapêutico , Neoplasias Ovarianas/radioterapia , Radiossensibilizantes/uso terapêutico , Ovinos , Compostos de ZincoRESUMO
Tissue damage in autoimmune diseases involves excessive production of reactive oxygen species (ROS) triggered by immune complexes (IC) and neutrophil (PMN) interactions via receptors for the Fc portion of IgG (FcgammaR) and complement receptors (CR). Modulation of both the effector potential of these receptors and ROS generation may be relevant to the maintenance of body homeostasis. In the present study, the modulatory effect of four flavonols (myricetin, quercetin, kaempferol, galangin) on rabbit PMN oxidative metabolism, specifically stimulated via FcgammaR, CR or both classes of receptors, was evaluated by luminol- and lucigenin-dependent chemiluminescence assays. Results showed that flavonol inhibitory effect was not dependent on the cell membrane receptor class stimulated but related to the lipophilicity of the compounds (their apparent partition coefficient values were obtained by high-performance liquid chromatography), and was also inversely related to the number of hydroxyl groups in the flavonol B ring and the ROS-scavenger activity (assessed by the luminol--H2O2--horseradish peroxidase reaction). Under the experimental conditions the flavonols tested were not toxic to PMNs (evaluated by lactate dehydrogenase release and trypan blue exclusion) and did not interfere with IC-induced phagocytosis (evaluated by transmission electron microscopy). Our results suggested that inhibition of IC-stimulated PMNs effector functions by the flavonols tested herein was the result of cooperation of different cellular mechanisms.