ROSANA SOUZA BANZATO
Projetos de Pesquisa
Unidades Organizacionais
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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- Effects of Eugenol and Dehydrodieugenol B from Nectandra leucantha against Lipopolysaccharide (LPS)-Induced Experimental Acute Lung Inflammation(2021) I, Marcia Bittencourt-Mernak; PINHEIRO, Nathalia M.; SILVA, Rafael C. da; PONCI, Vitor; BANZATO, Rosana; PINHEIRO, Aruana J. M. C. R.; OLIVO, Clarice R.; TIBERIO, Iolanda F. L. C.; LIMA NETO, Lidio G.; SANTANA, Fernanda P. R.; LAGO, Joao H. G.; PRADO, Carla M.Acute lung injury (ALI) is an important public health problem. The present work investigated whether dehydrodieugenol B treatment, a compound isolated from Brazilian plant Nectandra leucantha (Lauraceae), modulates experimental ALI and compared the observed effects to eugenol. Effects of dehydrodieugenol B in vitro in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were evaluated. The lung and systemic inflammatory profile, lung function, and possible mechanisms involved in BALB/C male mice (6-8 weeks) with ALI induced by LPS instillation (5 mg/kg) was assayed. Dehydrodieugenol B did not affect the cell viability and inhibited the increase in NO release and IL-1 beta and IL-6 gene expression induced by LPS. In vivo, both compounds reduced lung edema, inflammatory cells, and the IL-6 and IL-1 beta levels in bronchoalveolar lavage fluid, as well as reduced inflammatory cell infiltration and those positive to iNOS, MMP-9, and TIMP-1, and reduced the collagen content and the 8-isoprostane expression in lung tissue. Eugenol and dehydrodieugenol B also inhibited the phosphorylation of Jc-Jun-NH2 terminal Kinase (JNK), a signaling protein involved in the MAPKinase pathway. There was no effect of these compounds in lung function. Therefore, eugenol and dehydrodieugenol B ameliorates several features of experimental ALI and could be considered as a pharmacological tool to ameliorate acute lung inflammation.
- Long-term endogenous acetylcholine deficiency potentiates pulmonary inflammation in a murine model of elastase-induced emphysema(2021) BANZATO, Rosana; PINHEIRO, Nathalia M.; OLIVO, Clarice R.; SANTANA, Fernanda R.; LOPES, Fernanda D. T. Q. S.; CAPERUTO, Luciana C.; CAMARA, Niels O.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.; PRADO, Marco Antonio M.; PRADO, Vania F.; PRADO, Carla M.Acetylcholine (ACh), the neurotransmitter of the cholinergic system, regulates inflammation in several diseases including pulmonary diseases. ACh is also involved in a non-neuronal mechanism that modulates the innate immune response. Because inflammation and release of pro-inflammatory cytokines are involved in pulmonary emphysema, we hypothesized that vesicular acetylcholine transport protein (VAChT) deficiency, which leads to reduction in ACh release, can modulate lung inflammation in an experimental model of emphysema. Mice with genetical reduced expression of VAChT (VAChT KDHOM 70%) and wild-type mice (WT) received nasal instillation of 50 uL of porcine pancreatic elastase (PPE) or saline on day 0. Twenty-eight days after, animals were evaluated. Elastase instilled VAChT KDHOM mice presented an increase in macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage fluid and MAC2-positive macrophages in lung tissue and peribronchovascular area that was comparable to that observed in WT mice. Conversely, elastase instilled VAChT KDHOM mice showed significantly larger number of NF-kappa B-positive cells and isoprostane staining in the peribronchovascular area when compared to elastase-instilled WT-mice. Moreover, elastase-instilled VAChT-deficient mice showed increased MCP-1 levels in the lungs. Other cytokines, extracellular matrix remodeling, alveolar enlargement, and lung function were not worse in elastase-instilled VAChT deficiency than in elastase-instilled WT-controls. These data suggest that decreased VAChT expression may contribute to the pathogenesis of emphysema, at least in part, through NF-kappa B activation, MCP-1, and oxidative stress pathways. This study highlights novel pathways involved in lung inflammation that may contribute to the development of chronic obstrutive lung disease (COPD) in cholinergic deficient individuals such as Alzheimer's disease patients.
- Acute Lung Injury in Cholinergic-Deficient Mice Supports Anti-Inflammatory Role of alpha 7 Nicotinic Acetylcholine Receptor(2021) PINHEIRO, Nathalia M.; BANZATO, Rosana; TIBERIO, Iolanda; PRADO, Marco A. M.; PRADO, Vania F.; HAMOUDA, Ayman K.; PRADO, Carla M.(1) Background: The lung cholinergic pathway is important for controlling pulmonary inflammation in acute lung injury, a condition that is characterized by a sudden onset and intense inflammation. This study investigated changes in the expression levels of nicotinic and muscarinic acetylcholine receptors (nAChR and mAChR) in the lung during acute lung injury. (2) Methods: acute lung injury (ALI) was induced in wild-type and cholinergic-deficient (VAChT-KDHOM) mice using intratracheal lipopolysaccharide (LPS) instillation with or without concurrent treatment with nicotinic ligands. Bronchoalveolar lavage fluid was collected to evaluate markers of inflammation, and then the lung was removed and processed for isolation of membrane fraction and determination of acetylcholine receptors level using radioligand binding assays. (3) Results: LPS-induced increase in lung inflammatory markers (e.g., neutrophils and IL-1 beta) was significantly higher in VAChT-KDHOM than wild-type mice. In contrast, LPS treatment resulted in a significant increase in lung's alpha 7 nicotinic receptor level in wild-type, but not in VAChT-KDHOM mice. However, treatment with PNU 282987, a selective alpha 7 nicotinic receptor agonist, restored VAChT-KDHOM mice's ability to increase alpha 7 nicotinic receptor levels in response to LPS-induced acute lung injury and reduced lung inflammation. LPS also increased muscarinic receptors level in VAChT-KDHOM mice, and PNU 282987 treatment reduced this response. (4) Conclusions: Our data indicate that the anti-inflammatory effects of the lung cholinergic system involve an increase in the level of alpha 7 nicotinic receptors. Pharmacological agents that increase the expression or the function of lung alpha 7 nicotinic receptors have potential clinical uses for treating acute lung injury.