Navegando por Autor "Porto, Luís Cristovão de Moraes Sobrino"

Agora exibindo 1 - 7 de 7

Efeitos do licopeno in vitro e in vivo sobre o desequilíbrio redox e a inflamação pulmonar induzida pela exposição à fumaça de cigarro.
(2018) Rodrigues, Keila Karine Duarte Campos; Bezerra, Frank Silva; Bezerra, Frank Silva; Magalhães, Cíntia Lopes de Brito; Souza, Gustavo Henrique Bianco de; Porto, Luís Cristovão de Moraes Sobrino; Pedrosa, Maria Lúcia
O licopeno é um carotenóide com propriedades antioxidantes e anti-inflamatórias. Neste estudo, objetivou-se avaliar os efeitos in vitro e in vivo do licopeno na redução do desequilíbrio redox e na inflamação induzida pela exposição à fumaça do cigarro (FC). Para o estudo in vitro, as células J774A.1 (macrófagos) foram incubadas durante 3, 6 e 24 hs na presença de 0,5, 1,0 ou 2,0 μM de licopeno juntamente com um extrato de FC a 0,5% (EFC) e a geração de ERO intracelular foi mensurado. Para o estudo in vivo, 40 animais foram divididos em cinco grupos: um grupo de controle, exposto ao ar ambiente (GC), um grupo veículo que recebeu 200 μL de óleo de girassol por gavagem orogástrica (GO), um grupo exposto a FC, e dois grupos administrados com licopeno (diluído em óleo de girassol) nas doses de 25 ou 50 mg / kg / dia antes da exposição a FC (Li25 + FC e Li50 + FC). O tempo total dos experimentos foram de 5 e 60 dias. As concentrações de licopeno e o extrato da fumaça de cigarro (EFC) foram avaliados quanto á citotoxicidade, sendo que as concentrações de 8, 10 e 25 μM de licopeno nos tempos de 3, 6 e 24 horas apresentaram citotoxicidade, e as concentrações do EFC a partir de 0,63% até 10% também foram consideradas citotóxicas nos 3 tempos avaliados. Foi observado que as células tratadas com licopeno (1 μM ou 2 μM) e estimuladas com o EFC (0,5%) apresentaram uma diminuição da produção de ERO. No tempo de 3 horas o licopeno mimetizou o efeito do calfostin e DPI reduzindo a produção de ERO, desta forma sugere-se que o licopeno possa ter inibido uma ou ambas as vias relacionadas à produção de ERO, ou seja, PKC e/ou NADPH oxidase, respectivamente. Já em 24 horas, o licopeno não apresentou efeito modulatório sobre estas vias, uma vez que a produção de ERO foi igual as dos controles. O ensaios in vivo foram divididos em experimento a curto prazo (5 dias) e a longo prazo (60 dias), onde os camundongos foram administrados com licopeno e expostos à FC. No experimento a curto prazo, observamos um aumento no número de leucócitos totais, bem como da peroxidação lipídica, do dano ao DNA, do Vva, da translocação do Nrf2, da atividade de CAT, da razão GSH / GSSG e dos níveis de TNF-α, IFN-γ e IL-10 e a administração com licopeno foi capaz de suprimir este aumento. Em relação a Vvsa, o licopeno foi capaz de melhorar esse parâmetro, elevando a Vvsa. Em contraste, a atividade de SOD diminuiu no GFC em comparação com CG e administração com licopeno não alterou esse parâmetro. Já no experimento a longo prazo, o licopeno promoveu uma redução do número de leucócitos totais e dos parâmetros hematológicos, melhorou o quadro de enfisema pulmonar bem como o padrão histológico do parênquima pulmonar. O licopeno foi capaz de melhorar o desequilíbrio redox, diminuindo a peroxidação lipídica, o dano ao DNA e aumentou as atividades da SOD, CAT e o conteúdo de GSH, mas não apresentou diferença significativa em relação ao fator de transcrição Nrf2. Também foi observado uma diminuição dos níveis de TNF-α, IFN-γ e IL-10, bem como a atividade de MPO e o conteúdo de nitrito. Tomados em conjunto, nossos dados elucidam o papel do licopeno como um agente antioxidante e anti-inflamatório nos nossos modelos experimentais de exposição à FC.
Long-term exposure to cigarette smoke impairs lung function and increases HMGB-1 expression in mice.
(2011) Bezerra, Frank Silva; Valença, Samuel dos Santos; Pires, Karla Maria Pereira; Lanzetti, Manuella; Pimenta, Wagner Alves; Schmidt, Aline Cunha; Porto, Luís Cristovão de Moraes Sobrino; Zin, Walter Araújo
Cigarette smoke (CS)-induced emphysema is caused by a continuous inflammatory response in the lower respiratory tract. The development of the condition is believed to be mediated by oxidant–antioxidant imbalance. This paper describes the effects of long-term CS exposure on alveolar cell recruitment, antioxidant defense systems, activity of extracellular matrix metalloelastases, expression of metalloelastase MMP-12, and high mobility group box-1 protein (HMGB-1). Ten C57Bl/6 mice were exposed to 12 cigarettes-a-day for 60 consecutive days, while 10 control animals were exposed to ambient air. After sacrifice, bronchoalveolar lavage fluid (BALF) was removed, and lung tissue underwent biochemical and histological analyses. In CS-exposed animals influx of alveolar macrophages and neutrophils into BALF, lung static elastance, and expression of MMP-12 and HMGB-1 were significantly increased while the activity of antioxidant enzyme was significantly reduced in comparison with control group. Thus, we demonstrated for the first time that long-term CS exposure decreased antioxidant defenses concomitantly with impaired lung function, which was associated with HMGB-1 expression.
N-(2-mercaptopropionyl)-glycine but not Allopurinol prevented cigarette smoke-induced alveolar enlargement in mouse.
(2011) Pires, Karla Maria Pereira; Bezerra, Frank Silva; Machado, Mariana Nascimento; Zin, Walter Araújo; Porto, Luís Cristovão de Moraes Sobrino; Valença, Samuel dos Santos
We investigated the possible protective effects of the Allopurinol (A), N-(2-mercaptopropionyl)-glycine (M) and N-acetylcysteine (N) against lung injury caused by long-term exposure to cigarette smoke (CS) in mouse. C57BL6 mice were exposed to 12 cigarettes a day for 60 days and concomitantly treated with either one of the antioxidant drugs diluted in saline (CS + A—50 mg/kg; CS + M—200 mg/kg/day; CS + N—200 mg/kg/day). Control groups were sham-smoked (AA). Long-term CS exposure results in extensive parenchyma destruction in CS group. Both CS + N and CS + M groups showed preserved alveolar structure and showed preserved lung function when compared to CS group. Macrophage and neutrophil counts were decreased in CS + M, and CS + N groups when compared to CS group (p < 0.05). Antioxidant enzyme activities were reduced in all treated groups. CS + A showed the highest reduction in catalase activity (−25%, p < 0.01). We conclude that M treatment reduced long-term CS-induced inflammatory lung parenchyma destruction and lung function, comparable to N treatment, however, antioxidant administration did not reverse CS-induced antioxidant enzyme activity reduction.
Organ-related cigarette smoke-induced oxidative stress is strain-dependent.
(2010) Barroso, Carlos Romualdo Rueff; Trajano, Eduardo Tavares Lima; Alves, Jackson Nogueira; Paiva, Rojane Oliveira; Lanzetti, Manuella; Pires, Karla Maria Pereira; Bezerra, Frank Silva; Pinho, Ricardo Aurino; Valenca, Samuel Santos; Porto, Luís Cristovão de Moraes Sobrino
Background: Cigarette smoke (CS) is associated with oxidative stress in several organs because it contains high concentrations of free radicals and reactive oxygen species. Experimental models, using different strains, provide important insights into the genetic basis of diseases. This study sought to identify, in different mouse strains, the organ that is most-susceptible to CS-induced oxidative stress to obtain an optimized experimental animal model of oxidative injury induced by CS. Material/Methods: Male Swiss, DBA/2, C3H, BALB/c, and C57BL/6 mice were exposed to CS 3 times a day (4 cigarettes per session) for 60 consecutive days. Control groups from the same strains were sham-treated. Protein content, malondialdehyde level, myeloperoxidase activity, and nitrite level were assayed in lung, liver, kidney, and brain from all strains. Catalase and glutathione peroxidase activities were measured. Analyses of data were done by using a 1-way ANOVA with Bonferroni’s post-test (P<.05). Results: Cigarette smoke exposure resulted in distinct, organ-specific responses among strains. The survival rate of DBA/2 mice was lowest. BALB/c and C57BL/6 strains were more-susceptible to oxidative damage in the lung and liver. C3H and C57BL/6 mice were more-susceptible to oxidative damage in the brain. No renal oxidative damage was seen. Conclusions: Mouse strains and individual organs display a range of susceptibilities to CS-induced oxidative stress. BALB/c and C57BL/6 strains appear to be the best choices as experimental models for studying CS effects on liver and lung, and C3H and C57BL/6 strains for CS-effects on the brain.
Oxidative stress and inflammation in acute and chronic lung injuries.
(2023) Bezerra, Frank Silva; Lanzetti, Manuella; Nesi, Renata Tiscoski; Nagato, Akinori Cardozo; Silva, Cyntia Pecli e; Feitosa, Emanuel Kennedy; Melo, Adriana Correa; Cavalieri, Isabella Cattani; Porto, Luís Cristovão de Moraes Sobrino; Valença, Samuel dos Santos
Acute and chronic lung injuries are among the leading causes of mortality worldwide. Lung injury can affect several components of the respiratory system, including the airways, parenchyma, and pulmonary vasculature. Although acute and chronic lung injuries represent an enormous economic and clinical burden, currently available therapies primarily focus on alleviating disease symptoms rather than reversing and/or preventing lung pathology. Moreover, some supportive interventions, such as oxygen and mechanical ventilation, can lead to (further) deterioration of lung function and even the development of permanent injuries. Lastly, sepsis, which can originate extrapulmonary or in the respiratory system itself, contributes to many cases of lung-associated deaths. Considering these challenges, we aim to summarize molecular and cellular mechanisms, with a particular focus on airway inflammation and oxidative stress that lead to the characteristic pathophysiology of acute and chronic lung injuries. In addition, we will highlight the limitations of current therapeutic strategies and explore new antioxidant-based drug options that could potentially be effective in managing acute and chronic lung injuries.
The oxidative response of mouse hearts is modulated by genetic background.
(2013) Silva, Marco Aurélio dos Santos; Nagato, Akinori Cardozo; Trajano, Eduardo Tavares Lima; Alves, Jackson Nogueira; Bandeira, Ana Carla Balthar; Porto, Luís Cristovão de Moraes Sobrino; Bezerra, Frank Silva
Background: Smoking plays an important role in cardiovascular diseases. However, the reasons why some individuals develop those diseases and others do not remain to be explained. Objective: This study aimed at assessing the redox profile of the heart of different mouse strains after exposure to cigarette smoke. Methods: Male mice of the Swiss (n = 10), C3H (n = 10), BALB/c (n = 10) and C57BL/6 (n = 10) strains were exposed to cigarette smoke (12 cigarettes/day), while their respective controls (n = 10) were exposed to ambient air for 60 days. After being euthanized, their heart was removed for biochemical analyses. Results: Although the malondialdehyde content did not increase in any of the groups, catalase activity decreased in the Swiss (p < 0.05) and BALB/c (p < 0.05) strain mice as compared with their respective control groups, while myeloperoxidase decreased in the C3H (p < 0.05) and C57BL/6 (p < 0.001) strain mice as compared with their respective control groups. The reduced glutathione content decreased in the Swiss, C3H, C57BL/6 (p < 0.05) and BALB/c (p < 0,001) strain mice as compared with their respective control groups. Regarding reduced glutathione content, an increase was observed in the Swiss strain mice (p < 0.05), while a decrease was observed in the C3H (p < 0.05) and BALB/c (p < 0.001) strain mice as compared with their respective control groups. The reduced glutathione/reduced glutathione ratio showed a reduction in the Swiss and C57BL/6 (p < 0.05) strain mice as compared with their respective control groups. Conclusion: The genetic background of mice can influence the antioxidant response after exposure to cigarette smoke and seems to be a determinant factor for redox imbalance in Swiss and C57BL/6 strain mice. Understanding antioxidant responses and genetic background of C3H and BALB/c strain mice might provide important information regarding cardiac resistance to cigarette smoke.
Time course of inflammation, oxidative stress and tissue damage induced by hyperoxia in mouse lungs.
(2012) Nagato, Akinori Cardozo; Bezerra, Frank Silva; Lanzetti, Manuella; Lopes, Alan de Aguiar; Silva, Marco Aurélio dos Santos; Porto, Luís Cristovão de Moraes Sobrino; Valença, Samuel dos Santos
In this study our aim was to investigate the time courses of inflammation, oxidative stress and tissue damage after hyperoxia in the mouse lung. Groups of BALB⁄ c mice were exposed to 100% oxygen in a chamber for 12, 24 or 48 h. The controls were subjected to normoxia. The results showed that IL-6 increased progressively after 12 (P < 0.001) and 24 h (P < 0.001) of hyperoxia with a reduction at 48 h (P < 0.01), whereas TNF-a increased after 24 (P < 0.001) and 48 h (P < 0.001). The number of macrophages increased after 24 h (P < 0.001), whereas the number of neutrophils increased after 24 h (P < 0.01) and 48 h (P < 0.001). Superoxide dismutase activity decreased in all groups exposed to hyperoxia (P < 0.01). Catalase activity increased only at 48 h (P < 0.001). The reduced glutathione ⁄ oxidized glutathione ratio decreased after 12 h (P < 0.01) and 24 h (P < 0.05). Histological evidence of lung injury was observed at 24 and 48 h. This study shows that hyperoxia initially causes an inflammatory response at 12 h, resulting in inflammation associated with the oxidative response at 24 h and culminating in histological damage at 48 h. Knowledge of the time course of inflammation and oxidative stress prior to histological evidence of acute lung injury can improve the safety of oxygen therapy in patients.