EFEITO DA GENISTEÍNA NA FUNCIONALIDADE DE MACRÓFAGOS: UM ESTUDO COMPARATIVO ENTRE RATOS MACHOS E FÊMEAS

• Autor(a) principal: Juraszeck, Camila
• Data de Publicação: 2011
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UEPG
• Texto Completo: http://tede2.uepg.br/jspui/handle/prefix/961
• topic: dimorfismo sexual; 17-estradiol; fêmeas; fitoestrógenos; genisteína; macrófagos; 17-estradiol; females; genistein; macrophages; phytoestrogens, sexual; dimorphism; CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR

Genistein has estrogenic activity and can bind to estrogen receptors (ER), so it is considered a phytoestrogen. ER have been reported in macrophages and in that sense, the estrogens modulate immune responses. Despite the sexual dimorphism of the immune responses in females and males is well established, there are few studies that elucidate the role of bioactive compounds such as genistein among the genders. We investigated the effects of genistein on mice macrophage functionality, benchmarking males and females, which are divided into three groups according to sex and stage of the estrous cycle. First we checked the cytotoxicity,employing the technique of MTT reduction, in the following compounds: genistein, quercetin and 17-estradiol in the presence or absence of lipopolysaccharide (LPS). And none of these altered cell viability. To test the functionality of macrophages, the cells were treated for 24 h with two concentrations of genistein and quercetin (5M and 10M) as well as two concentrations of 17-estradiol (0,01 and 10 M), besides the control of the vehicle, the dimethylsulfoxide (DMSO) at 0,5%. The macrophages’ funtion standarts determined by spectrophotometry were the NO production in both basal and LPS induced, the production of H2O2 induced by LPS and by light microscopy was evaluated the phagocytic ability of macrophages, which were challenged to phagocytize Zymosan particles opsonized or not, after two hours of treatments. The results show a inhibition percentage of basal NO production in macrophages treated with genistein 10M, 34% and 40% for males and females in diestrus, respectively. In the macrophages obtained from females in proestrus quercetin treatment alone (in lower and higher concentration) showed a decrease in basal NO production significantly compared to control, with inhibition of 24% and 34% respectively. As NO production induced by LPS, macrophages from males showed significant inhibition of production with all treatments (except quercetin 5 μM), while in females in diestrus, treatments genistein (5 and 10 μM) and quercetin (5 and 10 μM ), this parameter significantly decreased functional macrophages, with values corresponding respectively to 25%, 30%, 17% and 31%. Once in females in proestrus, basal NO production induced by LPS and was inhibited only by quercetin (10M). All treatments of macrophages collected from the male reduced the production of H2O2 and genistein inhibition percentage of 10M of 27%. In females in diestrus was observed that treatment with genistein 5 e 10 M and quercetin 10M inhibited respectively 29%, 32% and 37% the production of H2O2. The H2O2 production by macrophages from females in proestrus was significantly inhibited by all treatments (except estradiol 0,01 ηM and quercetin 10M), and the percentage inhibition of genistein 5 e 10M was 22%. The phagocytic activity of macrophages was not affected by treatment with genistein for either group. Our results suggest that NO production, macrophages premodulated by exposure to 17-estradiol, the effect of genistein is less pronounced, may possible be explained by downregulation of ER in ex vivo treatments. In conclusion we can infer that, the use of genistein should account for sex, and therefore variations in serum hormone concentrations of 17-estradiol (sexual cycle) in females.