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Provedor de dados:  BJMBR
País:  Brazil
Título:  Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles
Autores:  Filip,A.G.
Clichici,S.
Daicoviciu,D.
Ion,R.M.
Tatomir,C.
Rogojan,L.
Opris,I.
Mocan,T.
Olteanu,D.
Muresan,A.
Data:  2011-01-01
Ano:  2011
Palavras-chave:  Photodynamic therapy
Oxidative stress
Apoptosis
Tetrapyrrolic macrocycles
Cytokines
Resumo:  Photodynamic therapy (PDT) mediated by oxidative stress causes direct tumor cell damage as well as microvascular injury. To improve this treatment new photosensitizers are being synthesized and tested. We evaluated the effects of PDT with 5,10,15,20-tetrakis(4-methoxyphenyl)-porphyrin (TMPP) and its zinc complex (ZnTMPP) on tumor levels of malondialdehyde (MDA), reduced glutathione (GSH) and cytokines, and on the activity of caspase-3 and metalloproteases (MMP-2 and -9) and attempted to correlate them with the histological alterations of tumors in 3-month-old male Wistar rats, 180 ± 20 g, bearing Walker 256 carcinosarcoma. Rats were randomly divided into five groups: group 1, ZnTMPP+irradiation (IR) 10 mg/kg body weight; group 2, TMPP+IR 10 mg/kg body weight; group 3, 5-aminolevulinic acid (5-ALA+IR) 250 mg/kg body weight; group 4, control, no treatment; group 5, only IR. The tumors were irradiated for 15 min with red light (100 J/cm², 10 kHz, 685 nm) 24 h after drug administration. Tumor tissue levels of MDA (1.1 ± 0.7 in ZnTMPP vs 0.1 ± 0.04 nmol/mg protein in control) and TNF-α (43.5 ± 31.2 in ZnTMPP vs 17.3 ± 1.2 pg/mg protein in control) were significantly higher in treated tumors than in controls. Higher caspase-3 activity (1.9 ± 0.9 in TMPP vs 1.1 ± 0.6 OD/mg protein in control) as well as the activation of MMP-2 (P < 0.05) were also observed in tumors. These parameters were correlated (Spearman correlation, P < 0.05) with the histological alterations. These results suggest that PDT activates the innate immune system and that the effects of PDT with TMPP and ZnTMPP are mediated by reactive oxygen species, which induce cell membrane damage and apoptosis.
Tipo:  Info:eu-repo/semantics/article
Idioma:  Inglês
Identificador:  http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011000100008
Editor:  Associação Brasileira de Divulgação Científica
Relação:  10.1590/S0100-879X2010007500140
Formato:  text/html
Fonte:  Brazilian Journal of Medical and Biological Research v.44 n.1 2011
Direitos:  info:eu-repo/semantics/openAccess
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