ABSTRACT
The physiological role of C-reactive protein (CRP), the classical acute-phase protein, is not well documented, despite many reports on biological effects of CRP in vitro and in model systems in vivo. It has been suggested that CRP protects mice against lethal toxicity of bacterial infections by implementing immunological responses. In Achatina fulica CRP is a constitutive multifunctional protein in haemolymph and considered responsible for their survival in the environment for millions of years. The efficacy of Achatina CRP (ACRP) was tested against both Salmonella typhimurium and Bacillus subtilis infections in mice where endogenous CRP level is negligible even after inflammatory stimulus. Further, growth curves of the bacteria revealed that ACRP (50 µg/mL) is bacteriostatic against gram negative salmonellae and bactericidal against gram positive bacilli. ACRP induced energy crises in bacterial cells, inhibited key carbohydrate metabolic enzymes such as phosphofructokinase in glycolysis, isocitrate dehydrogenase in TCA cycle, isocitrate lyase in glyoxylate cycle and fructose-1,6-bisphosphatase in gluconeogenesis. ACRP disturbed the homeostasis of cellular redox potential as well as reduced glutathione status, which is accompanied by an enhanced rate of lipid peroxidation. Annexin V-Cy3/CFDA dual staining clearly showed ACRP induced apoptosis-like death in bacterial cell population. Moreover, immunoblot analyses also indicated apoptosis-like death in ACRP treated bacterial cells, where activation of poly (ADP-ribose) polymerase-1 (PARP) and caspase-3 was noteworthy. It is concluded that metabolic impairment by ACRP in bacterial cells is primarily due to generation of reactive oxygen species and ACRP induced anti-bacterial effect is mediated by metabolic impairment leading to apoptosis-like death in bacterial cells.
Subject(s)
Animals , Anti-Bacterial Agents/pharmacology , Apoptosis/drug effects , Bacillus subtilis/drug effects , Bacillus subtilis/metabolism , C-Reactive Protein/isolation & purification , C-Reactive Protein/pharmacology , Gluconeogenesis/drug effects , Glycolysis/drug effects , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/metabolism , Gram-Negative Bacterial Infections/microbiology , Hemolymph/metabolism , Homeostasis/drug effects , Immunoblotting , Lipid Peroxidation/drug effects , Male , Mice , Oxidation-Reduction , Reactive Oxygen Species/metabolism , Salmonella Infections/drug therapy , Salmonella Infections/metabolism , Salmonella Infections/microbiology , Salmonella typhimurium/drug effects , Salmonella typhimurium/metabolism , SnailsABSTRACT
Achatina fulica C-reactive protein (ACRP) reversed the toxic effects of lead nitrate both in vivo in mice and in vitro in rat hepatocytes restoring the basal level of cell viability, lipid peroxidation, reduced glutathione and superoxides. Cytotoxicity was also significantly ameliorated in rat hepatocytes by in vitro pre-treatments with individual subunits (60, 62, 90 and 110 kDa) of ACRP. Annexin V-Cy3/CFDA dual staining showed significant reduction in the number of apoptotic hepatocytes pre-treated with ACRP. ACRP induced restoration of mitochondrial membrane potential was remarkable. ACRP pre-treatment prevented Pb-induced apoptosis mediated by caspase activation. The antagonistic effect of ACRP may be due to scavenging of reactive oxygen species which maintained the homeostasis of cellular redox potential as well as reduced glutathione status. The results suggest that ACRP crosses the species barrier and it may be utilized as a viable exogenous agent of cytoprotection against heavy metal related toxicity.
Subject(s)
Animals , Apoptosis/drug effects , Blotting, Western , C-Reactive Protein/pharmacology , Cell Survival , Cytoprotection/drug effects , Glutathione/metabolism , Hazardous Substances/toxicity , Hepatocytes/drug effects , Hepatocytes/pathology , Lead/toxicity , Lipid Peroxidation/drug effects , Male , Membrane Potential, Mitochondrial/drug effects , Mice , Mitochondria, Liver/drug effects , Mitochondria, Liver/pathology , Mollusca , Nitrates/toxicity , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolismABSTRACT
Antecedentes: La enfermedad periodontal (EP) es un factor de riesgo para desarrollar enfermedadescardiovasculares. Puede influir e iniciar una reacción autoinmune, aumentandola inflamación sistémica y acelerando la progresión de placas ateroescleróticas prexistentes.Ante inflamación aumenta la concentración de proteína C-reactiva (medida por PCR-us),que está relacionada con ateroesclerosis y riesgo cardiovascular. Se ha encontrado queel valor de PCR-us es significativamente mayor en pacientes con periodontitis. Objetivo:Determinar si existen diferencias significativas en los valores de PCR-us de pacientes conEP crónica entre moderada y avanzada no tratada y pacientes edéntulos totales comomarcador de ausencia de EP. Métodos: El diseño fue de casos y controles con una muestrade 60 pacientes mayores de 30 años de edad (30 casos con periodontitis crónica moderadaa avanzada y 30 controles edéntulos totales). Se tomó una muestra de sangre a todos lospacientes (cuadro hemático, colesterol, triglicéridos, glucemia, PCR-us) y se analizaron loshallazgos. Resultados: El promedio de PCR-us en los pacientes con periodontitis fue 2,19mg/L, y en los pacientes edéntulos, de 4,12 mg/L. Existe una tendencia a hallar valoresde PCR-us más elevados en pacientes edéntulos, al considerar que se encontró mayorexposición al riesgo en los pacientes con periodontitis. Los resultados no fueron estadísticamentesignificativos. Conclusión: La PCR-us se presentó más aumentada en los pacientesedéntulos totales y los valores de PCR-us en pacientes con periodontitis no se observaroncomo un factor de riesgo elevado para enfermedad cardiovascular...
Background: Periodontal disease (PD) is a risk factor for cardiovascular disease. It caninitiate an autoimmune reaction, increase systemic inflammation, and accelerate the progressionof preexisting atherosclerotic plaques. In presence of inflammation, PD increasesthe concentration of C-reactive protein (measured through hs-CRP) that is associated withatherosclerosis and cardiovascular risk. It has been found that the value of hs-CRP is significantlyhigher in patients with periodontitis. Objective: Determine if there are significantdifferences in the values of hs-CRP among patients with untreated moderate-to-advancedchronic PD and edentulous patients (marker of absence of PE). Methods: A case-controlstudy was carried out with a sample of 60 patients older than 30 years of age (30 cases withmoderate-to-advanced chronic periodontitis diagnosed and 30 edentulous controls). Bloodsamples were taken from all patients (complete blood count, cholesterol, triglycerides, glucose,hs-CRP) and the results were compared. Results: The average hs-CRP in patients withperiodontitis was 2.19 mg/L and 4.12 mg/L in edentulous patients. There is a tendency tofind values higher of hs-CRP in edentulous patients, given that there was higher exposure inpatients with periodontitis. The results were not statistically significant. Conclusion: hs-CRPwas higher in edentulous patients and hs-CRP values in patients with periodontitis were notseen as a high risk factor for cardiovascular disease..
Subject(s)
Atherosclerosis , Cardiovascular Diseases/diagnosis , Periodontal Diseases/diagnosis , C-Reactive Protein/administration & dosage , C-Reactive Protein/pharmacology , Oral Medicine , PeriodonticsABSTRACT
Introdução: O estudo foi desenvolvido com o objetivo de se avaliar o impacto do tratamento periodontal na condição do periodonto e na atividade inflamatória sistêmica dos pacientes portadores de lúpus eritematoso sistêmico (LES) e de periodontite. Material e métodos: seis portadores de LES e de periodontite foram submetidos à raspagem periodontal, com avaliação da condição periodontal, dos níveis séricos de PCR e da atividade de doença do LES antes e após o procedimento odontológico. Resultados: Após o tratamento periodontal, houve um aumento estatisticamente significativo da porcentagem média de sítios periodontais com profundidades de sondagem menores do que 4 mm e uma redução da porcentagem de tais sítios com profundidades de sondagem entre 4 mm e 6 mm, com placa bacteriana visível e sangramento à sondagem. Os valores médios anteriores e posteriores ao tratamento periodontal, referentes ao indicador sistêmico de atividade inflamatória PCR e à atividade de doença do LES, não apresentaram diferença estatisticamente significativa. Conclusões: Os dados observados no estudo sugerem que os portadores de LES respondem de forma adequada ao tratamento periodontal convencional. Além disso, tal tratamento realizado nos portadores de LES e de periodontite foi capaz de reduzir, em aproximadamente 30%, os níveis séricos de PCR. Esse dado sugere que a terapia periodontal atua sobre a resposta inflamatória sistêmica.
Introduction: The aim to assess the impact of the periodontal treatment on the periodontal condition and on the systemic inflammatory activity of patients who had systemic lupus erythematosus (SLE) and periodontitis. Material and methods: six patients with SLE e periodontitis received periodontal treatment, with assessment of the periodontal status, of the C-reactive protein serum levels and of the SLE disease activity before and after the periodontal treatment. Results: After periodontal treatment, the mean frequencies of periodontal sites with probing depths below 4 mm was elevated and with probing depths between 4 and 6 mm, with visible bacterial plaque and with bleeding on probing was reduced. These alterations were statistically significant. The mean values of Systemic Lupus Erythematosus Disease Activity Index and of the C-reactive protein serum levels didn't show statistically significant diferences. Conclusions: This study suggests that the patients with SLE answered adequately to periodontal treatment. Also, the conventional periodontal treatment was associated with a reduction of the C-reactive protein serum levels in approximately 30%, what suggests that the periodontal treatment influences the systemic inflammatory activity.
Subject(s)
Humans , Adult , Middle Aged , Periodontitis/therapy , C-Reactive Protein/pharmacology , Lupus Erythematosus, Systemic/physiopathology , Dental Scaling/instrumentation , Indicators (Statistics)ABSTRACT
Thirty-one patients bitten by venomous snakes in Botucatu area (State of Säo Paulo - Brazil), sixteen by Bothrops spp. and fifteen by Crotalus durissus terrificus, were studied. The group comprised twenty-nine males and two females, ranging from fourteen to sixty-three years of age (mean 33 ñ 15.Leukocytosis with neutrophilia and lymphopenia, increase of mucoproteins and C reactive protein, decrease of total serum protein and albumin, were observed on the first day after the accident. In addition, increased serum levels of the cytokines IL-6 and IL-8, but not of IL-1 beta and TNF-alpha, were observed. The alterations were generally more intense in patients bitten by Crotalus durissus terrificus than by Bothrops spp. It is concluded that these snakebite envenomations closely resemble an acute trauma, inducing a typical acute-phase response.