Protective effects of mito-TEMPO against doxorubicin cardiotoxicity in mice

Doxorubicin (DOX) is a chemotherapeutic that is widely used for the treatment of many human tumors. However, the development of cardiotoxicity has limited its use. The aim of the present study was to evaluate the possible efficacy of mito-TEMPO (mito-T) as a protective agent against DOX-induced cardiotoxicity in mice. C57BL/6 mice were treated twice with mito-T at low (5 mg/kg body weight) or high (20 mg/kg body weight) dose and once with DOX (24 mg/kg body weight) or saline (0.1 mL/20 g body weight) by means of intraperitoneal injections. The levels of malondialdehyde (MLDA), a marker of lipid peroxidation, and serum levels of creatine kinase were evaluated 48 h after the injection of DOX. DOX induced lipid peroxidation in heart mitochondria (p < 0.001), and DOX-treated mice receiving mito-T at low dose had levels of MLDA significantly lower than the mice that received only DOX (p < 0.01). Furthermore, administration of mito-T alone did not cause any significant changes from control values. Additionally, DOX-treated mice treated with mito-T at high dose showed decrease in serum levels of total CK compared to mice treated with DOX alone (p < 0.05). Our results indicate that mito-T protects mice against DOX-induced cardiotoxicity.Fundacao de Amparo a Pesquisa do Estado da Bahia-FAPESB, State Government of Bahia, BrazilFundacao Oswaldo Cruz, BrazilConselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq, Ministry of Science and Technology, BrazilFundacao Oswaldo Cruz, Goncallo Moniz Res Ctr, Rua Waldemar Falcao 121, BR-40296710 Salvador, BA, BrazilUniv Fed Sao Paulo, Lab Imunol Celular & Bioquim Fungos & Protozoario, Sao Paulo, BrazilUCL, London, EnglandUniv Fed Sao Paulo, Lab Imunol Celular & Bioquim Fungos & Protozoario, Sao Paulo, BrazilWeb of Scienc

Cellular therapy in Chagas' disease: potential applications in patients with chronic cardiomyopathy.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-04-17T17:08:11Z No. of bitstreams: 1 Soares MBP Cellular therapy....pdf: 1099345 bytes, checksum: b9cdc5c436ebb7787a5d5f669b8ef692 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-04-17T17:22:31Z (GMT) No. of bitstreams: 1 Soares MBP Cellular therapy....pdf: 1099345 bytes, checksum: b9cdc5c436ebb7787a5d5f669b8ef692 (MD5)Made available in DSpace on 2015-04-17T17:22:31Z (GMT). No. of bitstreams: 1 Soares MBP Cellular therapy....pdf: 1099345 bytes, checksum: b9cdc5c436ebb7787a5d5f669b8ef692 (MD5) Previous issue date: 2007Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, BrasilUniversidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Cardiologia de Laranjeiras. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, BrasilNearly a century after its discovery, Chagas' disease, caused by the protozoan Trypanosoma cruzi, remains a major health problem in Latin America. Although efforts in transmission control have contributed to a decrease in the number of new cases, approximately a third of chronic Chagasic individuals have or will develop the symptomatic forms of the disease, mainly cardiomyopathy. Chagas' disease is a progressively debilitating disease, which, at the final stages, there are no currently available treatments other than heart transplantation. In this scenario, cellular therapy is being tested as an alternative for millions of patients with heart dysfunction due to Chagas' disease. In this article, we review the studies of cellular therapy in animal models and in patients with Chagasic cardiomyopathy and the possible mechanisms by which cellular therapy may act in this disease

Exercise Training-Induced Changes in MicroRNAs: Beneficial Regulatory Effects in Hypertension, Type 2 Diabetes, and Obesity

MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally. They are involved in the regulation of physiological processes, such as adaptation to physical exercise, and also in disease settings, such as systemic arterial hypertension (SAH), type 2 diabetes mellitus (T2D), and obesity. In SAH, microRNAs play a significant role in the regulation of key signaling pathways that lead to the hyperactivation of the renin-angiotensin-aldosterone system, endothelial dysfunction, inflammation, proliferation, and phenotypic change in smooth muscle cells, and the hyperactivation of the sympathetic nervous system. MicroRNAs are also involved in the regulation of insulin signaling and blood glucose levels in T2D, and participate in lipid metabolism, adipogenesis, and adipocyte differentiation in obesity, with specific microRNA signatures involved in the pathogenesis of each disease. Many studies report the benefits promoted by exercise training in cardiovascular diseases by reducing blood pressure, glucose levels, and improving insulin signaling and lipid metabolism. The molecular mechanisms involved, however, remain poorly understood, especially regarding the participation of microRNAs in these processes. This review aimed to highlight microRNAs already known to be associated with SAH, T2D, and obesity, as well as their possible regulation by exercise training

Granulocyte colony-stimulating factor treatment in chronic Chagas disease: preservation and improvement of cardiac structure and function

Submitted by Martha Silveira Berbert ([email protected]) on 2011-04-13T05:38:28Z No. of bitstreams: 1 Granulocyte colony-stimulating factor treatment in.pdf: 1316507 bytes, checksum: 63c35205e5bb09d4d24366fe35a602bc (MD5)Made available in DSpace on 2011-04-13T05:38:28Z (GMT). No. of bitstreams: 1 Granulocyte colony-stimulating factor treatment in.pdf: 1316507 bytes, checksum: 63c35205e5bb09d4d24366fe35a602bc (MD5) Previous issue date: 2009-11Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Biologia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilThis study investigates the effects of granulocyte colony-stimulating factor (G-CSF) therapy in experimental chronic chagasic cardiomyopathy. Chagas disease is one of the leading causes of heart failure in Latin America and remains without an effective treatment other than cardiac transplantation. C57BL/6 mice were infected with 10(3) trypomastigotes of Trypanosoma cruzi, and chronic chagasic mice were treated with G-CSF or saline (control). Evaluations following treatment were functional, immunological, and histopathological. Comparing hearts of G-CSF-treated mice showed reduced inflammation and fibrosis compared to saline-treated chagasic mice. G-CSF treatment did not alter the parasite load but caused an increase in the number of apoptotic inflammatory cells in the heart. Cardiac conductance disturbances in all infected animals improved or remained stable due to the G-CSF treatment, whereas all of the saline-treated mice deteriorated. The distance run on a treadmill and the exercise time were significantly greater in G-CSF-treated mice when compared to chagasic controls, as well as oxygen consumption (VO(2)), carbon dioxide production (VCO(2)), and respiratory exchange ration (RER) during exercise. Administration of G-CSF in experimental cardiac ischemia had beneficial effects on cardiac structure, which were well correlated with improvements in cardiac function and whole animal performance

Green Tea Induces the Browning of Adipose Tissue—Systematic Review

Several foods and nutrients are being studied extensively because they have a positive effect on thermogenesis and the browning of white adipose tissue. Therefore, this study aims to evaluate, through a systematic review, the effect of green tea for inducing browning of adipose tissue. The systematic review was built following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyze. We searched the following electronic databases: PubMed (Medline), Science Direct, Scopus, and Web of Science. We included ten experimental articles that used green tea to treat induced obesity in rodents. Green tea reduced the weight of white and brown adipose tissue, positively regulated gene expression and microRNA that regulate the metabolism of adipose tissue, and morphological changes were identified as beige tissue. According to the results found, the factors involved in this induction to browning are PPARγ, PGC-1α, UCP1, CPT, and PRDM16. Therefore, green tea promotes the browning of adipose tissue in rodents. It is important to emphasize the need for studies in obese humans to identify whether the same metabolic response occurs

Transplantation of Adipose Tissue Mesenchymal Stem Cells in Experimental Chronic Chagasic Cardiopathy

BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi, is a major cause of heart failure in Latin America. Tissue therapy has been investigated as a possible therapeutic option for patients with cardiovascular disease. OBJECTIVE: This study evaluated the effects of therapy with mesenchymal stem cells in an experimental model of chronic Chagasic cardiomyopathy. METHODS: C57BL/6 mice were infected with 1000 trypomastigotes from the Colombian strain of T. cruzi and, after six months of infection, were treated with mesenchymal human stem cells from adipose tissue (STAT) or with Dulbecco/Vogt modified Eagle's minimal essential medium - DMEM (control). The treated group received two intraperitoneal injections of STAT (1x10(6) cells/dose), with a month interval between the two doses. Before and after the first and second months of treatment, the chagasic and normal control animals underwent cardiopulmonary exercise testing and electrocardiography. All animals were sacrificed under anesthesia after two months of treatment for histopathological analysis of the heart. RESULTS: No improvement was observed in arrhythmias and cardiovascular function in the group of animals treated with STAT; however, sections of mice hearts in this group revealed a significant reduction in the number of inflammatory cells (p<0.0001) and areas of fibrosis (p<0.01) in comparison with chagasic animals treated with DMEM. CONCLUSION: Thus, it is concluded that administration of intraperitoneal STAT can reduce inflammation and fibrosis in the heart of mice chronically infected with T. cruzi; however, there were no effects on the cardiac function two months after transplantation

Administration of granulocyte colony-stimulating factor induces immunomodulation, recruitment of T regulatory cells, reduction of myocarditis and decrease of parasite load in a mouse model of chronic Chagas disease cardiomyopathy.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-10-09T18:21:16Z No. of bitstreams: 1 Vasconcelos JF Administration....pdf: 1028504 bytes, checksum: cf15c623e7c8b011509bf0ed3eb8c71b (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2014-10-09T18:21:34Z (GMT) No. of bitstreams: 1 Vasconcelos JF Administration....pdf: 1028504 bytes, checksum: cf15c623e7c8b011509bf0ed3eb8c71b (MD5)Made available in DSpace on 2014-10-09T18:48:31Z (GMT). No. of bitstreams: 1 Vasconcelos JF Administration....pdf: 1028504 bytes, checksum: cf15c623e7c8b011509bf0ed3eb8c71b (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Estadual de Santa Cruz. Ilhéus, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasilospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilChagas disease, caused by Trypanosoma cruzi infection, is a leading cause of heart failure in Latin American countries. In a previous study, we showed beneficial effects of granulocyte colony-stimulating factor (G-CSF) administration in the heart function of mice with chronic T. cruzi infection. Presently, we investigated the mechanisms by which this cytokine exerts its beneficial effects. Mice chronically infected with T. cruzi were treated with human recombinant G-CSF (3 courses of 200 µg/kg/d for 5 d). Inflammation and fibrosis were reduced in the hearts of G-CSF-treated mice, compared with the hearts of vehicle-treated mice, which correlated with decreased syndecan-4, intercellular adhesion molecule-1, and galectin-3 expressions. Marked reductions in interferon-γ and tumor necrosis factor-α and increased interleukin-10 and transforming growth factor-ß were found after G-CSF administration. Because the therapy did not induce a Th1 to Th2 immune response deviation, we investigated the role of regulatory T (Treg) cells. A significant increase in CD3(+)Foxp3(+) cells was observed in the hearts of G-CSF-treated mice. In addition, a reduction of parasitism was observed after G-CSF treatment. Our results indicate a role of Treg cells in the immunosuppression induced by G-CSF treatment and reinforces its potential therapeutic use for patients with Chagas diseas

Characterization of cardiopulmonary function and cardiac muscarinic and adrenergic receptor density adaptation in C57BL/6 mice with chronic Trypanosoma cruzi infection.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-04-15T18:31:14Z No. of bitstreams: 1 Rocha N N Characterization of....pdf: 130180 bytes, checksum: d9995f076aa0e69d1ae1a91d9cadccc7 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-04-15T19:12:10Z (GMT) No. of bitstreams: 1 Rocha N N Characterization of....pdf: 130180 bytes, checksum: d9995f076aa0e69d1ae1a91d9cadccc7 (MD5)Made available in DSpace on 2015-04-15T19:12:10Z (GMT). No. of bitstreams: 1 Rocha N N Characterization of....pdf: 130180 bytes, checksum: d9995f076aa0e69d1ae1a91d9cadccc7 (MD5) Previous issue date: 2006Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Universidade Federal Fluminense. Niterói, RJ, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil /Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade do Estado do Rio de Janeiro. Rio de Janeiro, RJ, BrasilUniversidade do Estado do Rio de Janeiro. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil: Circulating antibodies in chagasic patients interact with myocardial beta adrenergic and muscarinic cholinergic receptors, triggering intracellular signals that alter cardiac function along the course of the disease. However, until now, experimental data in models of chronically infected chagasic mice linking the effects on myocardial beta adrenergic and muscarinic receptors to cardiopulmonary dysfunction is lacking. Thus, we studied C57BL/6 mice 8 months after intraperitoneal injection of 100 trypomastigote forms of the Colombian strain of T. cruzi. Uninfected mice, matched in age, were used as controls. Histopathological analyses (inflammation and fibrosis) and radio-ligand binding assays for estimation of muscarinic and adrenergic receptor density were performed in myocardium tissue samples. When compared to controls, infected mice had electrical conduction disturbances, diastolic dysfunction, lower O2 consumption and anaerobic threshold. In addition, hearts of chronic chagasic mice had intense inflammation and fibrosis, and decreased beta adrenergic and increased muscarinic receptor densities than normal controls. Our data suggest that chronic T. cruzi infection causes alterations in cardiac receptor density and fibrosis deposition which can be associated with cardiac conduction abnormalities, diastolic dysfunction and lower exercise capacity, associating for the first time all these functional and histopathological alterations in chagasic mic

Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-16T16:44:20Z No. of bitstreams: 1 Vasconcelos JF Therapeutic effects....pdf: 5296745 bytes, checksum: 1f932cf358f4ef9b9c7ab2a388430048 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-16T17:37:48Z (GMT) No. of bitstreams: 1 Vasconcelos JF Therapeutic effects....pdf: 5296745 bytes, checksum: 1f932cf358f4ef9b9c7ab2a388430048 (MD5)Made available in DSpace on 2017-08-16T17:37:49Z (GMT). No. of bitstreams: 1 Vasconcelos JF Therapeutic effects....pdf: 5296745 bytes, checksum: 1f932cf358f4ef9b9c7ab2a388430048 (MD5) Previous issue date: 2017National Council for Scientific and Technological Development (CNPq) and Bahia Research Foundation (FAPESB).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Salvador. Escola de Ciências da Saúde. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Federal de Bahia. Instituto de Ciências da Saúde. Departamento de Bioquímica e Biofísica. Salvador, BA, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Centro de Ciências da Saúde. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilChagas disease cardiomyopathy is a parasite-driven inflammatory disease to which there are no effective treatments. Here we evaluated the therapeutic potential of N,N-dimethylsphingosine(DMS), which blocks the production of sphingosine-1-phosphate(S1P), a mediator of cellular events during inflammatory responses, in a model of chronic Chagas disease cardiomyopathy. DMS-treated, Trypanosoma cruzi-infected mice had a marked reduction of cardiac inflammation, fibrosis and galectin-3 expression when compared to controls. Serum concentrations of galectin-3, IFNγ and TNFα, as well as cardiac gene expression of inflammatory mediators were reduced after DMS treatment. The gene expression of M1 marker, iNOS, was decreased, while the M2 marker, arginase1, was increased. DMS-treated mice showed an improvement in exercise capacity. Moreover, DMS caused a reduction in parasite load in vivo. DMS inhibited the activation of lymphocytes, and reduced cytokines and NO production in activated macrophage cultures in vitro, while increasing IL-1β production. Analysis by qRT-PCR array showed that DMS treatment modulated inflammasome activation induced by T. cruzi on macrophages. Altogether, our results demonstrate that DMS, through anti-parasitic and immunomodulatory actions, can be beneficial in the treatment of chronic phase of T. cruzi infection and suggest that S1P-activated processes as possible therapeutic targets for the treatment of Chagas disease cardiomyopathy