ABSTRACT
PURPOSE: To investigate the anti-inflammatory effects of simvastatin in rats undergoing one-lung ventilation (OLV) followed by lung re-expansion. METHODS: Male Wistar rats (n=30) were submitted to 1-h OLV followed by 1-h lung re-expansion. Treated group received simvastatin (40 mg/kg for 21 days) previous to OLV protocol. Control group received no treatment or surgical/ventilation interventions. Measurements of pulmonary myeloperoxidase (MPO) activity, pulmonary protein extravasation, and serum levels of cytokines and C-reactive protein (CRP) were performed. RESULTS: OLV significantly increased the MPO activity in the collapsed and continuously ventilated lungs (31% and 52% increase, respectively) compared with control (p<0.05). Treatment with simvastatin significantly reduced the MPO activity in the continuously ventilated lung but had no effect on lung edema after OLV. The serum IL-6 and CRP levels were markedly higher in OLV group, but simvastatin treatment failed to affect the production of these inflammatory markers. Serum levels of IL-1β, TNF-α and IL-10 remained below the detection limit in all groups. CONCLUSIONS: In an experimental one-lung ventilation model pre-operative treatment with simvastatin reduces remote neutrophil infiltration in the continuously ventilated lung. Our findings suggest that simvastatin may be of therapeutic value in OLV-induced pulmonary inflammation deserving clinical investigations.
Subject(s)
Animals , Male , Rats , Anti-Inflammatory Agents/pharmacology , Neutrophil Infiltration/drug effects , One-Lung Ventilation/methods , Simvastatin/pharmacology , Anti-Inflammatory Agents/therapeutic use , C-Reactive Protein/analysis , Cytokines/blood , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lung/drug effects , Lung/physiopathology , Models, Animal , Peroxidase/physiology , Random Allocation , Rats, Wistar , Reproducibility of Results , Simvastatin/therapeutic use , Thoracic Surgical Procedures/adverse effects , Thoracic Surgical Procedures/methodsABSTRACT
A mieloperoxidase (MPO) é uma enzima derivada de leucócitos que catalisa a formação de numerosas espécies reativas oxidantes. Além de integrantes da resposta imune inata, evidências têm comprovado a contribuição desses oxidantes para o dano tecidual durante inflamação. A MPO participa de atividades biológicas pró-aterogênicas relacionadas à evolução da doença cardiovascular, incluindo iniciação, propagação e as fases de complicação aguda do processo aterosclerótico. Dessa forma, a MPO e sua cascata inflamatória representam um alvo atrativo para investigação prognóstica e terapêutica na doença aterosclerótica cardiovascular. Nesta revisão, apresentamos o estado da arte no entendimento das ações biológicas às evidências clínicas da relação entre MPO e doença arterial coronariana. Vários estudos apontam para o efeito independente dos níveis de MPO na evolução da doença e ocorrência de eventos em pacientes com síndrome coronariana aguda. Entretanto, ainda não é consistente o valor preditivo adicional dos níveis de MPO na estratificação de risco cardiovascular para incorporá-la à prática clínica como sinalizadora de vulnerabilidade de placa. Estudos adicionais são necessários para confirmar seu papel nas diferentes formas de apresentação da cardiopatia isquêmica, além da padronização do ensaio, ponto fundamental para a transição desse marcador do ambiente de pesquisa para uso na rotina clínica.
Myeloperoxidase (MPO) is an enzyme derived of leukocytes that catalyze formation of numerous reactive oxidant species. Besides members of the innate host defense, evidences have been proving the contribution of these oxidants to tissue injury during inflammation. MPO participates in proatherogenic biological activities related to the evolution of cardiovascular disease, including initiation, propagation and acute complications of atherosclerotic process. Thereby, MPO and its inflammatory cascade represents an attractive target for prognostical investigation and therapeutics in atherosclerotic cardiovascular disease. In this review, we present the state of the art in the understanding of biological actions to clinical evidences of the relationship between MPO and coronary arterial disease. Several studies point to the independent effect of MPO levels in the evolution of disease and incidence of events in patients with acute coronary syndrome. However, the additional predictive value of MPO levels in the cardiovascular risk assessment, to incorporate it to the clinical practice as marker of plaque vulnerability, is still not consistent. Additional studies are necessary to confirm its role in the different forms of presentation of ischemic disease, besides the standardization of the assay, fundamental point for transition of this marker from research atmosphere to use in clinical routine: : from laboratory to clinical practice.
Subject(s)
Humans , Cardiovascular Diseases , Peroxidase/physiology , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/enzymology , Acute Coronary Syndrome/etiology , Arteriosclerosis/diagnosis , Arteriosclerosis/enzymology , Arteriosclerosis/etiology , Biomarkers/blood , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/enzymology , Cardiovascular Diseases/etiology , Coronary Artery Disease/diagnosis , Coronary Artery Disease/enzymology , Coronary Artery Disease/etiology , Lipid Metabolism , Nitric Oxide/metabolism , Prognosis , Peroxidase/blood , Peroxidase/deficiencyABSTRACT
Este trabajo describe y analiza los principales factores antimicrobianos no inmunoglobulínicos de la saliva, su función biológica, interacciones y relación con diversas situaciones fisiológicas y patológicas que pueden presentarse en la cavidad bucal. Finalmente, se reseñan algunas aplicaciones clinicoterapéuticas de estos factores, destacando la necesidad de nuevas investigaciones destinadas a probar otros tratamientos que contribuyan a incrementar la efectividad de los sistemas innatos de defensa