ABSTRACT
Many pathological conditions linked to cigarette smoking are caused by the production of reactive oxygen species (ROS). The present study was conducted to analyze the effect of ROS on the lungs of Swiss mice exposed to cigarette smoking, focusing on autophagy-mediated mechanisms, and investigate the involvement of SESN2, AMPK, and mTOR signaling. Mice were exposed to cigarette smoke (CS) for 7, 15, 30, 45, and 60 days; the control group was not exposed to CS. Only mice exposed to CS for 45 days were selected for subsequent N-acetylcysteine (NAC) supplementation and smoke cessation analyses. Exposure to CS increased the production of ROS and induced molecular changes in the autophagy pathway, including an increase in phosphorylated AMPK and ULK1, reduction in phosphorylated mTOR, and increases in SESN2, ATG12, and LC3B levels. NAC supplementation reduced ROS levels and reversed all molecular changes observed upon CS treatment, suggesting the involvement of oxidative stress in inducing autophagy upon CS exposure. When exposure to CS was stopped, there were decreases in the levels of oxidative stress, AMPK and ULK1 phosphorylation, and autophagy-initiating molecules and increase in mTOR phosphorylation. In conclusion, these results suggest the involvement of ROS, SESN2, AMPK, and mTOR in the CS-induced autophagic process in the lung.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Autophagy/drug effects , Cell Cycle Proteins/metabolism , Cigarette Smoking/adverse effects , Oxidative Stress/drug effects , TOR Serine-Threonine Kinases/metabolism , Animals , Blotting, Western , Electrophoresis, Polyacrylamide Gel , Male , Mice , Peroxidases/metabolism , Reactive Oxygen Species/metabolismABSTRACT
O infarto agudo do miocárdio (IAM) é uma situação clínica determinada por processo isquêmicoagudo, que resulta em necrose miocárdica. Os marcadores cardíacos em caso de isquemia reversível, atualmente,apresentam sensibilidade limitada.Objetivo: Verificar a sensibilidade da albumina modificada isquêmica (AMI), como marcador cardíaco. Métodos: Estudo experimental, realizado no Laboratório de Experimentação Animal da Universidade Regional Integrada (URI), Erechim, RS, no período de 2011 a 2013. Após a indução isquêmica do miocárdio em ratos da linhagem Wistar-Tecpar, com idade aproximada entre 60-90 dias, através da administração de isoproterenol hidrocloridrato, o conteúdo da AMI foi avaliado em diferentes tempos. Resultados: Os valores da AMI mantiveram-se diminuídos durante as três horas iniciais, após a indução isquêmica pelo isoproterenol hidrocloridrato. Conclusão: Neste estudo, a albumina modificada pela isquemia foi considerada um marcador sensível,principalmente nas três horas iniciais da isquemia...
Background: Acute myocardial infarction (AMI) is a condition determined by an acute ischemic process resulting in myocardial necrosis. Cardiac markers in reversible ischemia currently have limited sensitivity. Objective: To check the sensitivity of ischemia modified albumin (IMA) as a cardiac marker.Methods: Experimental study held at the Animal Experimentation Laboratory of Universidade Regional Integrada (URI), Erechim, RS, from 2011 to 2013. After myocardial ischemic induction in Wistar-Tecpar rats aged about 60-90 days through administration of isoproterenol hydrochloride, the IMA content was evaluated at different times. Results: The IMA values remained reduced during the three first hours after ischemic induction by isoproterenol hydrochloride.Conclusion: In this study, ischemia modified albumin was considered a sensitive marker, particularly in the first three hours of ischemia...
Subject(s)
Animals , Rats , Albumins , Myocardial Ischemia/complications , Myocardial Ischemia/physiopathology , Rats, Wistar , Sensitivity and Specificity , Analysis of Variance , Animal Experimentation , Cardiovascular Diseases/mortality , Myocardial Infarction/epidemiology , Myocardial Infarction/physiopathology , Isoproterenol/administration & dosage , Treatment Outcome , Histological Techniques/methods , Troponin I/administration & dosageABSTRACT
Objetivos: Verificar a toxicidade em ratos Wistar expostos ao formaldeídeo a 10% e Complucad®, analisando-se as enzimas hepáticas alaninaaminotransferase e aspartatoaminotransferase, os tecidos pulmonar, renal e hepático, após período de exposição aguda. Métodos. A amostra contou com 24 ratos machos adultos, da linhagem Wistar-Tecpar, divididos aleatoriamente em três grupos com oito animais cada. O Grupo Controle Negativo (G.C), não foi exposto às substâncias. O Grupo Controle Positivo (G.F) foi exposto ao formaldeído a 1.33 ppm e o Grupo Experimental (G.CP) exposto à substância Complucad®. Os animais foram mantidos sob condições normais de temperatura, com fotoperíodo de 12h claro/escuro, alimentados com ração balanceada para roedores e água ad libitum, sendo expostos diariamente (8 horas/dia) às respectivas substâncias. Após o período de exposição os mesmos foram anestesiados para coleta sanguínea, seguida de eutanásia para coleta dos tecidos. Resultados: O teste ANOVA seguido de TUKEY realizado com nível de significância de 5% demonstrou para a enzima alanina diferença (p=0,04) entre o G.F quando comparado ao controle. A enzima aspartato apresentou (p=0,20). A avaliação histológica dos órgãos demonstrou alteração significativa para o tecido hepático sendo (p=0,0001), tecido pulmonar (p=0,0085) e tecido renal (p=0,00), mediante o teste estatístico com Qui-Quadrado. Através da aplicação do teste Kruskall Wallis 5% para as variáveis dos tecidos, observou-se infiltração de células e perda da arquitetura (p<0,03), dilatação alveolar (p=0,01), tumefação celular cortical, congestão vascular cortical e dilatação tubular (p<0,01). Conclusão: Houve grau de toxicidade aos referidos xenobióticos, sendo em maior intensidade no grupo exposto ao formaldeídeo a 10%.
Objectives: Verify the toxicity in Wistar rats exposed to formaldehyde solutions at 10% and Complucad®, analyzing the alaninaaminotransferase/aspartatoaminotransferase hepatic enzymes and the lung, kidney and liver tissues, after a sharp period of exposition. Methods: The 24 Wistar-Tecpar adult male rats, divided randomly into three groups, with eight animals each group. The Negative Control Group (G.C) was not exposed to the substances; the Positive Control Group (G.F) was exposed to formaldehyde at 1.33 ppm, and the Experimental Group (G. CP) was exposed to Complucad®. The animals were kept under room temperature, in a 12 hour light/dark photo period, fed with a balanced diet for rodents and ad libitum water, being daily exposed (8 hours a day) to the respective substances. After a period of exposition, they were anesthetized for blood collection, then the euthanasia for tissue collection. Results: the ANOVA followed by TUKEY performed with a significance level of 5% showed for enzyme alanine (p=0,04) between the G.F compared with the control group. The enzyme aspartate, showed (p=0,20). The organs histological evaluation showed a significant alteration for the liver tissue, being (p=0,0001), lung tissue (p=0,085), and kidney tissue (p=0.00), before treatment with the Qui-Quadrado Test. Applying the test Kruskall Wallis 5% for the variables of the tissues, observed, cell infiltration and loss of architecture (p=0,03), dilated alveolar (p=0,01), cortical cell swelling, cortical vascular congestion and dilatation tubular (p<0,01). Conclusion: There was a degree of toxicity to the referred xenobiotic, being more intense on the group exposed to formaldehyde at 10%.
