Protective role of chlorogenic acid on DNA damage caused by ochratoxin A exposure

Chlorogenic acid (ChlA) has shown short-term protective effects against the cytogenotoxiceffects of ochratoxin A (OTA). The present study evaluated the effect of oraladministration of ChlA in male Wistar rats exposed to OTA. OTA (0.4 mg/kg bw/day), ChlA (5 mg/kg bw/day), or the combination of both, were administered orally toanimals during 28 days. No deaths, decrease in feed consumption or change in the bodyweight of animals were observed in any group. In the OTA-treated group a decrease inlocomotion as well as increased DNA damage in blood, kidney and bone marrow cellswere observed. ChlA alone was not genotoxic for animals. The combination of OTA+ChlA decreased the DNA damage by 37% in blood cells, by 55% in kidney cells andby 80% in bone marrow cells compared to OTA-treated group. In conclusion, oraltreatment with ChlA showed a good protective effect on genotoxicity produced byOTA in rats during 28 days exposure.El ácido clorogé nico (ChlA) mostró efectos protectores a corto plazo contra los efectos citogenotóxicos de ocratoxina A (OTA). En el presente estudio se evaluó si este polifenol mantiene su efecto protector mediante la administración oral en ratas Wistar machos expuestas a OTA. OTA (0,4 mg/kg/día), ChlA (5 mg/kg/día), o la combinación de ambos, fueron administrados a los animales por vía oral durante 28 días. No se observaron muertes, ni disminución en el consumo de alimento, ni cambios en el peso corporal en ningún grupo de animales. En el grupo tratado con OTA se observó disminución en la locomoción, así como daño en el ADN en las cé lulas de sangre, riñó n y mé dula ósea. En los animales que solo recibieron ChlA no se observaron efectos genotóxicos. La combinación de OTA + ChlA disminuyó el daño del ADN en un 37%en las cé lulas sanguíneas, en un 55% en las cé lulas renales y en un 80% en las cé lulas de la mé dula ósea con respecto al grupo tratado con OTA. En conclusión, el tratamiento oral con ChlA mostró buen efecto protector sobre la genotoxicidad producida por OTA en ratas durante 28 días de exposición.Fil: Campra, Noelia Anahí. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Biotecnología Ambiental y Salud - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Biotecnología Ambiental y Salud; ArgentinaFil: Cariddi, Laura Noelia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Biotecnología Ambiental y Salud - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Biotecnología Ambiental y Salud; ArgentinaFil: Escobar, Franco Matias. Universidad Nacional de Río Cuarto; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Sabini, Maria Carola. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Biotecnología Ambiental y Salud - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Biotecnología Ambiental y Salud; ArgentinaFil: Freire de lima, Celio Geraldo. Universidade Federal do Rio de Janeiro; BrasilFil: Decote Ricardo, Debora. Universidade Federal do Rio de Janeiro; BrasilFil: Roma, Dardo Andrés. Universidad Nacional de Río Cuarto; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Mañas, Fernando Javier. Universidad Nacional de Río Cuarto; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Dalcero, Ana Maria. Universidad Nacional de Río Cuarto; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Rol protector del ácido clorogénico sobre el daño del ADN causado por la exposición a ocratoxina A

Chlorogenic acid (ChlA) has shown short-term protective effects against the cytogenotoxic effects of ochratoxin A (OTA). The present study evaluated the effect of oral administration of ChlA in male Wistar rats exposed to OTA. OTA (0.4 mg/kg bw/ day), ChlA (5 mg/kg bw/day), or the combination of both, were administered orally to animals during 28 days. No deaths, decrease in feed consumption or change in the body weight of animals were observed in any group. In the OTA-treated group a decrease in locomotion as well as increased DNA damage in blood, kidney and bone marrow cells were observed. ChlA alone was not genotoxic for animals. The combination of OTA +ChlA decreased the DNA damage by 37% in blood cells, by 55% in kidney cells and by 80% in bone marrow cells compared to OTA-treated group. In conclusion, oral treatment with ChlA showed a good protective effect on genotoxicity produced by OTA in rats during 28 days exposure.El ácido clorogénico (ChlA) mostró efectos protectores a corto plazo contra los efectos citogenotóxicos de ocratoxina A (OTA). En el presente estudio se evaluó si este polifenol mantiene su efecto protector mediante la administración oral en ratas Wistar machos expuestas a OTA. OTA (0,4 mg/kg/día), ChlA (5 mg/kg/día), o la combinación de ambos, fueron administrados a los animales por vía oral durante 28 días. No se observaron muertes, ni disminución en el consumo de alimento, ni cambios en el peso corporal en ningún grupo de animales. En el grupo tratado con OTA se observó disminución en la locomoción, así como daño en el ADN en las células de sangre, riñón y médula ósea. En los animales que solo recibieron ChlA no se observaron efectos genotóxicos. La combinación de OTA + ChlA disminuyó el daño del ADN en un 37%en las células sanguíneas, en un 55% en las células renales y en un 80% en las células de la médula ósea con respecto al grupo tratado con OTA. En conclusión, el tratamiento oral con ChlA mostró buen efecto protector sobre la genotoxicidad producida por OTA en ratas durante 28 días de exposición.Facultad de Ciencias Veterinaria

2-Chloro-4,6-bis{(E)-3-methoxy-4-[(4-methoxybenzyl)oxy]styryl}pyrimidine: Synthesis, Spectroscopic and Computational Evaluation

A novel curcumin analog namely 2-chloro-4,6-bis{(E)-3-methoxy-4-[(4-methoxybenzyl)oxy]- styryl}pyrimidine (compound 7) was synthesized by three-step reaction. The condensation reaction of protected vanillin with 2-chloro-4,6-dimethylpyrimidine (6) was the most efficient step, resulting in a total yield of 72%. The characterization of compound 7was performed by 1Hand 13C nuclearmagnetic resonance (NMR), as well as high-resolution mass spectrometry. The experimental spectrometric data were compared with the theoretical spectra obtained by the density functional theory (DFT) method, showing a perfectmatch between them.UV-visible spectroscopy and steady-state fluorescence emission studies were performed for compound 7 in solvents of different polarities and the results were correlated with DFT calculations. Compound 7 showed a solvatochromism effect presenting higher molar extinction coefficient (log " = 4.57) and fluorescence quantum yield ( = 0.38) in toluene than in acetonitrile or methanol. The simulation of both frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP) suggested that the experimental spectra profile in toluene was not interfered by a possible charge transfer. These results are an indication of a low probability of compound 7 in reacting with unsaturated phospholipids in future applications as a fluorescent dye in biological systems

2-Nitro-1-vinyl-1H-imidazole

Nitroimidazoles are pharmacophoric groups responsible for important antiparasitic activity against several infectious diseases. 2-Nitroimidazoles are found in some antiparasitic drugs and are one of the main moieties responsible for the biological activities exhibited. As an example, we can mention the drug benznidazole, the only drug available in Brazil for the treatment of Chagas disease. This work describes an efficient methodology for the synthesis of 2-nitro-1-vinyl-1H-imidazole through a simple and direct approach, as well as its full characterization and biological assessment. The antiparasitic evaluation of 2-nitro-1-vinyl-1H-imidazole against Trypanosoma cruzi (Tulahuen C2C4-LacZ strain) showed IC50 = 4.8 μM on amastigotes and low cytotoxicity against LLC-MK2 cells (IC50 > 500 μM), validating 2-nitro-1-vinyl-1H-imidazole as a biologically active structural subunit for anti-T. cruzi activity. The results presented herein demonstrate that 2-nitro-1-vinyl-1H-imidazole can be easily obtained, possessing great potential for use in the design of new antichagasic drugs through a molecular hybridization strategy using known coupling reactions

2-Nitro-1-vinyl-1<i>H</i>-imidazole

Nitroimidazoles are pharmacophoric groups responsible for important antiparasitic activity against several infectious diseases. 2-Nitroimidazoles are found in some antiparasitic drugs and are one of the main moieties responsible for the biological activities exhibited. As an example, we can mention the drug benznidazole, the only drug available in Brazil for the treatment of Chagas disease. This work describes an efficient methodology for the synthesis of 2-nitro-1-vinyl-1H-imidazole through a simple and direct approach, as well as its full characterization and biological assessment. The antiparasitic evaluation of 2-nitro-1-vinyl-1H-imidazole against Trypanosoma cruzi (Tulahuen C2C4-LacZ strain) showed IC50 = 4.8 μM on amastigotes and low cytotoxicity against LLC-MK2 cells (IC50 > 500 μM), validating 2-nitro-1-vinyl-1H-imidazole as a biologically active structural subunit for anti-T. cruzi activity. The results presented herein demonstrate that 2-nitro-1-vinyl-1H-imidazole can be easily obtained, possessing great potential for use in the design of new antichagasic drugs through a molecular hybridization strategy using known coupling reactions

Cellular Stress and Senescence Induction during <i>Trypanosoma cruzi</i> Infection

Chagas disease (CD) is a neglected tropical disease caused by Trypanosoma cruzi infection that, despite being discovered over a century ago, remains a public health problem, mainly in developing countries. Since T. cruzi can infect a wide range of mammalian host cells, parasite–host interactions may be critical to infection outcome. The intense immune stimulation that helps the control of the parasite’s replication and dissemination may also be linked with the pathogenesis and symptomatology worsening. Here, we discuss the findings that support the notion that excessive immune system stimulation driven by parasite persistence might elicit a progressive loss and collapse of immune functions. In this context, cellular stress and inflammatory responses elicited by T. cruzi induce fibroblast and other immune cell senescence phenotypes that may compromise the host’s capacity to control the magnitude of T. cruzi-induced inflammation, contributing to parasite persistence and CD progression. A better understanding of the steps involved in the induction of this chronic inflammatory status, which disables host defense capacity, providing an extra advantage to the parasite and predisposing infected hosts prematurely to immunosenescence, may provide insights to designing and developing novel therapeutic approaches to prevent and treat Chagas disease

Immune Responses in Leishmaniasis: An Overview

Leishmaniasis is a parasitic, widespread, and neglected disease that affects more than 90 countries in the world. More than 20 Leishmania species cause different forms of leishmaniasis that range in severity from cutaneous lesions to systemic infection. The diversity of leishmaniasis forms is due to the species of parasite, vector, environmental and social factors, genetic background, nutritional status, as well as immunocompetence of the host. Here, we discuss the role of the immune system, its molecules, and responses in the establishment, development, and outcome of Leishmaniasis, focusing on innate immune cells and Leishmania major interactions

Immunomodulatory Role of Capsular Polysaccharides Constituents of Cryptococcus neoformans

Submitted by Sandra Infurna ([email protected]) on 2020-03-19T15:25:32Z No. of bitstreams: 1 MariseNunes_AlexandreMorrot_etal_IOC_2019.pdf: 281134 bytes, checksum: 889971e7c48db82f9ec1e4b6c01ce3c7 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2020-03-19T15:41:09Z (GMT) No. of bitstreams: 1 MariseNunes_AlexandreMorrot_etal_IOC_2019.pdf: 281134 bytes, checksum: 889971e7c48db82f9ec1e4b6c01ce3c7 (MD5)Made available in DSpace on 2020-03-19T15:41:09Z (GMT). No. of bitstreams: 1 MariseNunes_AlexandreMorrot_etal_IOC_2019.pdf: 281134 bytes, checksum: 889971e7c48db82f9ec1e4b6c01ce3c7 (MD5) Previous issue date: 2019Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Seropédica, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Seropédica, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Cryptococcosis is a systemic fungal infection caused by Cryptococcus neoformans. In immunocompetent patients, cryptococcal infection is often confined to the lungs. In immunocompromised individuals, C. neoformans may cause life-threatening illness, either from novel exposure or through reactivation of a previously acquired latent infection. For example, cryptococcal meningitis is a severe clinical disease that can manifest in people that are immunocompromised due to AIDS. The major constituents of the Cryptococcus polysaccharide capsule, glucuronoxylomannan (GXM), and galactoxylomannan (GalXM), also known as glucuronoxylomanogalactan (GXMGal), are considered the primary virulence factors of Cryptococcus. Despite the predominance of GXM in the polysaccharide capsule, GalXM has more robust immunomodulatory effects on host cellular immunity. This review summarizes current knowledge regarding host-Crytococcus neoformans interactions and the role of capsular polysaccharides in host immunomodulation. Future studies will likely facilitate a better understanding of the mechanisms involved in antigenic recognition and host immune response to C. neoformans and lead to the development of new therapeutic pathways for cryptococcal infection

Canine Macrophage DH82 Cell Line As a Model to Study Susceptibility to Trypanosoma cruzi Infection

Submitted by Sandra Infurna ([email protected]) on 2017-07-05T13:58:03Z No. of bitstreams: 1 marise_nunes_etal_IOC_2017.pdf: 1246095 bytes, checksum: 548f464ca2e48448d7a0f90ad7b62711 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-07-05T14:12:11Z (GMT) No. of bitstreams: 1 marise_nunes_etal_IOC_2017.pdf: 1246095 bytes, checksum: 548f464ca2e48448d7a0f90ad7b62711 (MD5)Made available in DSpace on 2017-07-05T14:12:11Z (GMT). No. of bitstreams: 1 marise_nunes_etal_IOC_2017.pdf: 1246095 bytes, checksum: 548f464ca2e48448d7a0f90ad7b62711 (MD5) Previous issue date: 2017Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Seropédica, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Seropédica, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Seropédica, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Seropédica, RJ, Brasil.Trypanosoma cruzi is an obligatory intracellular protozoan parasite, and it is the etiological agent of Chagas' disease that is endemic in the Americas. In addition to humans, a wide spectrum of mammals can be infected by T. cruzi, including dogs. Dogs develop acute and chronic disease, similar to human infection. T. cruzi can infect almost all cell types and after cell invasion, the metacyclics trypomastigotes localize in the cytoplasm, where they transform into amastigotes, the replicative form of T. cruzi in mammals. After amastigote multiplication and differentiation, parasites lyse host cells and spread through the body by blood circulation. In this work, we evaluated the in vitro ability of T. cruzi to infect a canine macrophage cell line DH82 compared with RAW264.7, a murine tissue culture macrophage. Our results have shown that the T. cruzi is able to infect, replicate and differentiate in DH82 cell line. We observed that following treatment with LPS and IFN-γ DH82 cells were more resistant to infection and that resistance was not related reactive oxygen species production in our system. In this study, we also found that DH82 cells became more susceptible to T. cruzi infection when cocultured with apoptotic cells. The analysis of cytokine production has showed elevated levels of the TGF-β, IL-10, and TNF-α produced by T. cruzi-infected canine macrophages. Additionally, we demonstrated a reduced expression of the MHC class II and CD80 by infected DH82 cell line

Capsular polysaccharides from Cryptococcus neoformans modulate production of neutrophil extracellular traps (NETs) by human neutrophils

Submitted by Sandra Infurna ([email protected]) on 2019-09-03T17:15:08Z No. of bitstreams: 1 MariseNunes_SuzanaCReal_etal_IOC_2019.pdf: 1108627 bytes, checksum: ca75434d43f19d081589da7931f232b0 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-09-03T17:25:23Z (GMT) No. of bitstreams: 1 MariseNunes_SuzanaCReal_etal_IOC_2019.pdf: 1108627 bytes, checksum: ca75434d43f19d081589da7931f232b0 (MD5)Made available in DSpace on 2019-09-03T17:25:23Z (GMT). No. of bitstreams: 1 MariseNunes_SuzanaCReal_etal_IOC_2019.pdf: 1108627 bytes, checksum: ca75434d43f19d081589da7931f232b0 (MD5) Previous issue date: 2015Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Seropédica, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de janeiro, RJ, Brasil.In the present study, we characterized the in vitro modulation of NETs (neutrophil extracellular traps) induced in human neutrophils by the opportunistic fungus Cryptococcus neoformans, evaluating the participation of capsular polysaccharides glucuronoxylomanan (GXM) and glucuronoxylomannogalactan (GXMGal) in this phenomenon. The mutant acapsular strain CAP67 and the capsular polysaccharide GXMGal induced NET production. In contrast, the wild-type strain and the major polysaccharide GXM did not induce NET release. In addition, C. neoformans and the capsular polysaccharide GXM inhibited PMA-induced NET release. Additionally, we observed that the NET-enriched supernatants induced through CAP67 yeasts showed fungicidal activity on the capsular strain, and neutrophil elastase, myeloperoxidase, collagenase and histones were the key components for the induction of NET fungicidal activity. The signaling pathways associated with NET induction through the CAP67 strain were dependent on reactive oxygen species (ROS) and peptidylarginine deiminase-4 (PAD-4). Neither polysaccharide induced ROS production however both molecules blocked the production of ROS through PMA-activated neutrophils. Taken together, the results demonstrate that C. neoformans and the capsular component GXM inhibit the production of NETs in human neutrophils. This mechanism indicates a potentially new and important modulation factor for this fungal pathogen