RESUMO
The aim of this study is to examine the ability of resveratrol to counteract hexavalent chromium [Cr(VI)]-induced genetic damage, as well as the possible pathways associated with this protection. Hsd:ICR male mice are divided into groups of the following five individuals each: (a) control 1, distilled water; (b) control 2, ethanol 30%; (c) resveratrol, 50 mg/kg by gavage; (d) CrO3, 20 mg/kg intraperitoneally; (e) resveratrol + CrO3, resveratrol administered 4 h prior to CrO3. The assessment is performed on peripheral blood. Micronuclei (MN) kinetics are measured from 0 to 72 h, while 8-hydroxydeoxyguanosine (8-OHdG) adduct repair levels, endogenous antioxidant system biomarkers, and apoptosis frequency were quantified after 48 h. Resveratrol reduces the frequency of Cr(VI)-induced MN and shows significant effects on the 8-OHdG adduct levels, suggesting that cell repair could be enhanced by this polyphenol. Concomitant administration of resveratrol and Cr(VI) results in a return of the activities of glutathione peroxidase and catalase to control levels, accompanied by modifications of superoxide dismutase activity and glutathione levels. Thus, antioxidant properties might play an important role in resveratrol-mediated inhibition of Cr(VI)-induced oxidant genotoxicity. The increase in apoptotic cells and the decrease in necrosis further confirmed that resveratrol effectively blocks the actions of Cr(VI).
Assuntos
Cromo , Dano ao DNA , 8-Hidroxi-2'-Desoxiguanosina , Animais , Antioxidantes/farmacologia , Cromo/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , Resveratrol/farmacologiaRESUMO
Toxoplasma gondii disseminates and causes congenital infection by invasion of the endothelial cells. The aim of this study was to analyze the ability of two strains to invade two endothelial cell types. Tachyzoites of the RH and ME49 strains were expanded in Balb/c and C57BL6-RAG2-/- mice, respectively. Tachyzoites were harvested from 72 h Vero cell cultures and incubated for 30 min to 4 h at 10:1 parasite/cell ratio in 24-well plates, containing monolayers of either HMEC-1 line or human umbilical cells (HUVECs). The number of infected cells and parasitic vacuoles per infected cell were counted in Wright stained slides. A slow increase in the proportion of infected cells occurred but varied according to cell type-parasite strain combination: ME49 tachyzoites invaded up to 63% HMEC-1 cells, while RH parasites infected up to 19% HUVECs. ME49 and RH tachyzoites invaded 49 and 46% HUVECs and HMEC-1 cells, respectively. Reinvasion and formation of new parasitophorous vacuoles of infected cells was more frequent than invasion of noninfected cells. The results support that the factors influencing invasion, and thus dissemination and vertical transmission, are parasite type, host cell type/subtype, and activation state. Interestingly, T. gondii virulence does not seem to relay on its invasion efficiency, but probably on replication speed.
Assuntos
Células Endoteliais/parasitologia , Toxoplasma/fisiologia , Animais , Células Cultivadas , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Chagas' disease contributes significantly to cardiovascular morbidity and mortality in several Latin-American countries. Previous studies have reported the effect of the human leukocyte antigen (HLA) molecules in the immune response regulation of Trypanosoma cruzi infection, and the association of HLA antigens with heart damage. We studied the major histocompatibility complex (MHC) class I (HLA-A and HLA-B), and class II (HLA-DR) genes in a sample of 66 serologically positive individuals with and without cardiomyopathy, and in 127 healthy controls. The total group of seropositive individuals revealed increased frequencies of HLA-B39 (pc=4.3x10(-5), odds ratio [OR]=3.35) and DR4 (pc=1.8x10(-5), OR=2.91) when compared to healthy controls. Increased frequencies of HLA-A68 and HLA-B39 were found in asymptomatic individuals when compared to patients with cardiomyopathy (pc=0.014, OR=4.99 and pc=0.001, OR=4.46, respectively). Also, patients with cardiomyopathy exhibited increased frequency of HLA-B35 when compared to healthy controls (pc=0.048, OR=2.56). The HLA-DR16 frequency was increased in patients with cardiomyopathy compared with asymptomatic individuals (pc=0.05, OR=No determined) and healthy controls (pc=0.02, OR=5.0). The results suggest that MHC alleles might be associated with the development of chronic infection and with heart damage in Chagas' disease. HLA-DR4 and HLA-B39 could be associated directly with the infection by T. cruzi, whereas, HLA-DR16 could be marker of susceptibility to heart damage and HLA-A68 might confer protection to develop cardiomyopathy.