Nandrolone androgenic hormone presents genotoxic effects in different cells of mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Experimental infection with Leishmania chagasi in immunosuppressed Balb/c mice: cytokines and parasite burdens

The immune response in leishmaniasis may result in a polarization of the T lymphocyte subpopulation, altering cell phenotype and resulting in immune protection or disease exacerbation. Leishmania may persist in the body either during asymptomatic infections or after treatment, which represents high risk under immunosuppression. The objective of this study was to evaluate the effect of infection with immunosuppression by dexamethasone associated with pentoxifylline on animal weight, spleen weight, spleen and hepatic parasitic load and immunopathology, as well as the IFN-gamma and IL-10 production in spleen cell culture of Balb/c mice infected with Leishmania chagasi. The infection did not cause body weight gain in animals, but both the weight and size of the spleen were increased. The immunosuppression using dexamethasone associated with pentoxifylline affected body weight gain and spleen weight and size in both infected and non-infected animals. The immunosuppression did not significantly alter the course of the splenic or hepatic parasite burden. Dexamethasone and pentoxifylline significantly affected cytokine production, but did not influence the Th1/Th2 ratio in infected animals.

Organ tropism during the acute and chronic phases of Trypanosoma cruzi infection in BALB/c mice

The aim of the present study was to investigate the presence of Trypanosoma cruzi in the heart, liver, lung, and kidneys, using hemoculture and PCR analysis, of mice infected with different parasite strains during the acute and chronic phases of infection. Parasitemia curves revealed strain-specific biological behaviors. For the Y and JLP strains, the acute phase of infection started at days six and ten post-infection, parasitemia peaked at days seven and 15 post-infection, the chronic phase started at days nine and 28 post-infection, and animals started dying at days 19 and 120 post-infection, respectively. When the two strains were compared, the JLP strain exhibited reduced and slower replication rates associated with a delayed peak of parasitism and reduced parasite burdens. However, parasites were detected in all studied organs using PCR analysis. The capacity of both strains to infect different organs likely influences disease pathogenesis.

Experimental infection of Leishmania chagasi in immunosuppressed balb/c mice: cellular immune response and parasite burden

The immune response to leishmaniasis can result in a polarization of a subpopulation of T lymphocytes, which leads to a different cell phenotype and results in immune protection or exacerbation of the disease. Leishmanias persist in the body both in asymptomatic infections and after treatment, representing risks in terms of immunosuppression. The objective of this study was to evaluate the effects of infection and immunosuppression by dexamethasone associated with pentoxifylline on animal weight, spleen weight, the parasitic load in the spleen and liver, as well as the production of IFN-gamma and IL-10 in spleen cell culture of Balb/c mice infected with Leishmania chagasi. The infection did not alter animal weight gain, but spleen weight and size increased. The immunosuppression, induced by dexamethasone associated with pentoxifylline, affected animal weight gain and weight and size of the spleen (in infected and not infected animals). The immunosuppression did not significantly alter the course of the parasite burden in the spleen and liver. Dexamethasone and pentoxifylline affected the studied cytokine production, but not influenced on Th1/Th2 response in infected animals.

Black bean (Phaseolus vulgaris L.) as a protective agent against DNA damage in mice

This study was designed to evaluate the toxicogenetic or protective effect of cooked and dehydrated black beans (Phaseolus vulgaris L.) in bone marrow and peripheral blood cells of exposed mice. The frequency of micronuclei detected using the bone marrow erythrocyte micronucleus test and level of DNA lesions detected by the comet assay were chosen as end-points reflecting mutagenic and genotoxic damage, respectively. Initially, Swiss male mice were fed with a 20% black bean diet in order to detect mutagenic and genotoxic activity. However, no increase in the frequency of bone marrow micronucleated polychromatic erythrocytes (MN PCEs) or DNA lesion in leukocytes was observed. In contrast, received diets containing 1, 10 or 20% of black beans, a clear, but not dose-dependent reduction in the frequency of MN PCEs were observed in animals simultaneously treated with cyclophosphamide, an indirect acting mutagen. Similar results were observed in leukocytes by the comet assay. Commercial anthocyanin was also tested in an attempt to identify the bean components responsible for this protective effect. However, instead of being protective, the flavonoid, at the highest dose administered (50 mg/kg bw), induced primary DNA lesion, as detected by the comet assay. These data indicate the importance of food components in preventing genetic damage induced by chemical mutagens, and also reinforce the role of toxicogenetic techniques in protecting human health. (C) 2003 Elsevier Ltd. All rights reserved.

Experimental paracoccidioidomycosis in high and low antibody responder mice of Selection IV-A

High (H) and low (L) responder mice were selected for their ability to produce antibodies against sheep and human erythrocytes (Selection IV-A). In this selection, the difference in antibody responsiveness between H and L lines (HIV-A and LIV-A mice, respectively) was shown to depend mainly on macrophage function. The more rapid catabolism of antigens by macrophages in L mice has been suggested as the main cause of the low antibody production. Due to this high macrophage activity, L animals have been described as more resistant than H animals to intracellular pathogens. These animals were utilized as an experimental model of paracoccidioidomycosis. HIV-A and LIV-A mice were infected with Paracoccidioides brasiliensis by the intravenous route. As expected, H mice were more susceptible to P. brasiliensis with a shorter survival time and higher levels of specific antibodies when compared to L mice. Contrasting with the survival time, the lungs, spleen and liver from H mice showed typical nodular granulomas containing epithelioid and giant cells and few fungi. on the other hand, in LN-A mice, the lesions of these organs were characterized by looser granulomas with irregular borders and the presence of a large number of fungi, However, the adrenal gland showed different lesion patterns. In H mice these lesions were extensive and characterized by loose granulomas with numerous fungi, while in LIV-A mice the lesions were small and limited to the cortex. Moreover the HIV-A mice presented higher levels of serum corticosterone when compared to LIV-A ones. The higher susceptibility of H mice could be attributed to the extensive lesions of the adrenal glands. These results suggest the use of the H line from the IV-A Selection as an experimental model for further studies of adrenal involvement in paracoccidioidomycosis.

Modifying Effects of Lemongrass Essential Oil on Specific Tissue Response to the Carcinogen N-Methyl-N-Nitrosurea in Female BALB/c Mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Protective effects of lemongrass (Cymbopogon citratus STAPF) essential oil on DNA damage and carcinogenesis in female Balb/C mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of cytokines concentration and percentage of survival of rabies virus-infected mice submitted to anti-rabies Vero-cell propagated vaccine and P-acnes

Previously, survival of rabies infection was shown to correlate with low IL-6 serum concentration in mice subjected to post-exposure treatment with the Fuenzalida Palacios rabies vaccine in conjunction with the immunomodulator Propionibacterium acnes, previously Corynebacterium parvum. Considering the substitution of the Fuenzalida Palacios rabies vaccine by the Vero cell raised anti-rabies vaccine in almost all countries, the objective of this work was to evaluate the survival and cytokine serum concentration of rabies virus-infected mice treated with P. acnes in conjunction with or the anti-rabies-VERO vaccine. For this, Swiss mice were experimentally infected with street rabies virus and subjected to vaccine and/or P. acnes following infection. Animals were killed at different times and serum was collected to evaluate cytokines. The greatest survival was observed in animals given one or two does of P. acnes in the absence of vaccination. Animals given anti-rabies VERO vaccine alone or with three doses of P. acnes had the second highest survival rate. The group that had the highest percentage of mortality also had the highest IL-6 concentration on the 10th day, a time correlating with clinical symptoms of the animals. The results reinforce the inefficacy of anti-rabies vaccine in only one dose as a post-exposure treatment irrespective of the type of vaccine used, the immunomodulation activity of P. acnes in rabies post-exposure treatment and suggest a role for IL-6 in rabies virus pathogenesis. (c) 2006 Elsevier B.V. All rights reserved.

Effect of vaccination and the immunomodulators bacillus of Calmette-Guerin, Avridine and Propionibacterium acnes on rabies in mice

Responses: of vaccination and treatment to immunomodulators against rabies in mice were evaluated through macrophage inhibition factor (MIF), intra-pad inoculation (IPI) and serum neutralization (SN) tests and by the detection of gamma-interferon (IFN-gamma). Onco-BCG, Avridine and Propionibacterium acnes were administered to groups of mice. Higher survival rates were found in animals treated with P. acnes. Lower levels of IFN-gamma were observed in the groups of infected and vaccinated mice. The IPI was not effective on detecting the response of delayed-type hypersensitivity. Vaccine induced in the infected animals a more intense response to MIF reaction. (C) 1998 Elsevier B.V. Ltd. All rights reserved.

Increased interleukin-10 associated with low IL-6 concentration correlated with greater survival rates in mice infected by rabies virus vaccinated against it and immunomodulated with P-acnes

Macrophage activity, cytokines serum concentration, serum neutralizing antibodies and lethality by rabies were evaluated in swiss mice experimentally infected with street rabies virus and submitted or not to antirabies vaccination and immunomodulation with P. acnes. Animals were killed at different times and serum was collected in order to evaluate cytokines concentration; peritonial and splenic macrophages were collected for macrophage activity evaluation. Greater survival rates higher IL-10 and low IL-6 serum concentration were observed in vaccinated animals treated using P. acnes. (C) 2004 Elsevier Ltd. All rights reserved.

Natural killer activity in mice infected with rabies virus and submitted to P-acnes (Propionibacterium acnes) as immunomodulator

The natural killer (NK) activity and lethality were evaluated in swiss mice experimentally infected with street rabies virus and submitted to immunomodulation by P. acnes (formerly Corynebacterium parvum). The infected animals were sacrificed at different times and spleen non-adherent cells were obtained through ficoll-hypaque gradient and depletion of glass-adherent cells. Immunosuppression was observed in rabies virus infected mice correlated with lower NK activity in clinically ill animals. Higher NK activity and percentual of survival were observed in the group submitted to P. acnes. The increased survival correlated with higher NK activity induced by P. acnes suggests a protective role of this natural barrier against rabies virus infection in mice. (C) 2000 Elsevier B.V. Ltd. All rights reserved.

Distribution of rabies virus in infected mice, vaccinated and submitted to P-acnes as immunomodulator

The lethality and distribution of rabies virus were evaluated in swiss mice experimentally infected with street rabies virus, vaccinated and submitted to immunomodulation by P. acnes (formerly Corynebacterium parvum). The animals were sacrificed at different times,when the different tissues were collected and submitted to fluorescent antibody test (FAT) and mouse inoculation test (MIT). The group submitted to vaccination and P. acnes treatment presented a percentage of survival superior to that observed in infected mice only treated with P. acnes. Control infected animals had the lowest survival rates. The distribution of rabies virus in spleen of infected mice, vaccinated and submitted to P. acnes was superior to that verified in infected mice not treated with P. acnes. The increased survival correlated with the distribution of rabies virus in lymphoid tissues, could be interpreted as the consequence of P. acnes activity on macrophages. The results suggest the role of macrophages against rabies virus infection in mice and the importance of vaccination in the post expositive treatment of rabies. (C) 2002 Published by Elsevier B.V. Ltd.

The protective effects of Baypamun®HK in mice experimentally infected with Toxoplasma gondii

O presente trabalho teve como objetivo verificar os efeitos do Baypamun®HK sobre a sobrevida de camundongos albinos, experimentalmente infectados com Toxoplasma gondii amostra RH, submetidos ou não ao tratamento com sulfadiazina-pirimetamina, bem como sobre a formação e número de cistos cerebrais. Quatro grupos de 20 camundongos foram inoculados com 10(5) taquizoítos, via subcutânea, e submetidos a diferentes tratamentos. Os testes sorológicos foram realizados pela técnica de imunofluorescência indireta, e, dos animais que sucumbiram, amostras de cérebro, pulmão e fígado foram retiradas para exame citológico e de cérebros para a pesquisa de cistos. Ao final de 60 dias todos os sobreviventes foram sacrificados. Isoladamente o Baypamun®HK não apresentou uma ação protetora contra a infecção pelo T. gondii, mas sua associação com o tratamento específico pela sulfadiazina-pirimetamina promoveu maior sobrevida dos animais e uma resposta de anticorpos mais intensa e duradoura.

Effect of Mikania glomerata (Asteraceae) leaf extract combined with anti-venom serum on experimental Crotalus durissus (Squamata: Viperidae) envenomation in rats

Crotalic envenomation represents the highest number of deaths when compared to other snakebite envenomations of medical interest. Crotalic venom has important characteristics such as neurotoxicity, myotoxicity, nephrotoxicity, and clotting and hemolytic action. We evaluated the clinical and laboratory aspects of Crotalus durissus terrificus experimental envenomation in Wistar rats treated with antivenom and the aqueous extract of the plant mikania glomerata. The animals were divided into three groups: Group C (control); Group VS-venom and antivenom; Group VSM-venom, antivenom and aqueous extract of M glomerata. Crotalic poison caused clinical and laboratory alterations in Wistar mice. Significant clinical alterations were: temperature decrease, edema in the venom inoculated member, sedation and a locomotion decrease in groups VS and VSM when compared with group C. A faster recovery from sedation was observed only for animals of group VSM when compared to VS. There was an increase in the number of leukocytes, neutrophils and creatine kinase in the VS and VSM groups, compared to group C. Wistar rats showed a high resistance to crotalic venom. Additional studies with different doses, time of treatment, different administration methods and histopathological and immunological studies are necessary to understand the action of M glomerata in crotalic accidents. Rev. Biol. Trop. 57 (4): 929-937. Epub 2009 December 01.