scholarly journals Redefining control O2 conditions for rat medullary slices via quantification of oxidative and nitrosative stress: experiments in the caudal solitary complex (cSC)

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Geoffrey Ciarlone ◽  
Michael Matott ◽  
Carol Landon ◽  
Jay Dean
2016 ◽  
Vol 311 (6) ◽  
pp. C1027-C1039 ◽  
Author(s):  
Geoffrey E. Ciarlone ◽  
Jay B. Dean

Central CO2 chemoreceptive neurons in the caudal solitary complex (cSC) are stimulated by hyperoxia via a free radical mechanism. Hyperoxia has been shown to increase superoxide and nitric oxide in the cSC, but it remains unknown how changes in Pco2 during hyperoxia affect the production of O2-dependent reactive oxygen and nitrogen species (RONS) downstream that can lead to increased levels of oxidative and nitrosative stress, cellular excitability, and, potentially, dysfunction. We used real-time fluorescence microscopy in rat brain slices to determine how hyperoxia and hypercapnic acidosis (HA) modulate one another in the production of key RONS, as well as colorimetric assays to measure levels of oxidized and nitrated lipids and proteins. We also examined the effects of CO2 narcosis and hypoxia before euthanasia and brain slice harvesting, as these neurons are CO2 sensitive and hypothesized to employ CO2/H+ mechanisms that exacerbate RONS production and potentially oxidative stress. Our findings show that hyperoxia ± HA increases the production of peroxynitrite and its derivatives, whereas increases in Fenton chemistry are most prominent during hyperoxia + HA. Using CO2 narcosis before euthanasia modulates cellular sensitivity to HA postmortem and enhances the magnitude of the peroxynitrite pathway, but blunts the activity of Fenton chemistry. Overall, hyperoxia and HA do not result in increased production of markers of oxidative and nitrosative stress as expected. We postulate this is due to antioxidant and proteosomal removal of damaged lipids and proteins to maintain cell viability and avoid death during protracted hyperoxia.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Aderville Cabassi ◽  
Simone Maurizio Binno ◽  
Stefano Tedeschi ◽  
Gallia Graiani ◽  
Cinzia Galizia ◽  
...  

Rationale. Heart failure (HF) is accompanied by the development of an imbalance between oxygen- and nitric oxide-derived free radical production leading to protein nitration. Both chlorinating and peroxidase cycle of Myeloperoxidase (MPO) contribute to oxidative and nitrosative stress and are involved in tyrosine nitration of protein. Ceruloplasmin (Cp) has antioxidant function through its ferroxidase I (FeOxI) activity and has recently been proposed as a physiological defense mechanism against MPO inappropriate actions.Objective. We investigated the relationship between plasma MPO-related chlorinating activity, Cp and FeOxI, and nitrosative stress, inflammatory, neurohormonal, and nutritional biomarkers in HF patients.Methods and Results. In chronic HF patients (n=81, 76±9 years, NYHA Class II (26); Class III (29); Class IV (26)) and age-matched controls (n=17, 75±11 years, CTR), plasma MPO chlorinating activity, Cp, FeOxI, nitrated protein, free Malondialdehyde, BNP, norepinephrine, hsCRP, albumin, and prealbumin were measured. Plasma MPO chlorinating activity, Cp, BNP, norepinephrine, and hsCRP were increased in HF versus CTR. FeOxI, albumin, and prealbumin were decreased in HF. MPO-related chlorinating activity was positively related to Cp (r= 0.363,P<0.001), nitrated protein, hsCRP, and BNP and inversely to albumin.Conclusions. Plasma MPO chlorinated activity is increased in elderly chronic HF patients and positively associated with Cp, inflammatory, neurohormonal, and nitrosative parameters suggesting a role in HF progression.


Author(s):  
Marietta Zita Poles ◽  
László Juhász ◽  
Mihály Boros

AbstractMammalian methanogenesis is regarded as an indicator of carbohydrate fermentation by anaerobic gastrointestinal flora. Once generated by microbes or released by a non-bacterial process, methane is generally considered to be biologically inactive. However, recent studies have provided evidence for methane bioactivity in various in vivo settings. The administration of methane either in gas form or solutions has been shown to have anti-inflammatory and neuroprotective effects in an array of experimental conditions, such as ischemia/reperfusion, endotoxemia and sepsis. It has also been demonstrated that exogenous methane influences the key regulatory mechanisms and cellular signalling pathways involved in oxidative and nitrosative stress responses. This review offers an insight into the latest findings on the multi-faceted organ protective activity of exogenous methane treatments with special emphasis on its versatile effects demonstrated in sepsis models.


2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Alexander Franz ◽  
Laura Joseph ◽  
Constantin Mayer ◽  
Jan-Frieder Harmsen ◽  
Holger Schrumpf ◽  
...  

Osteoarthritis (OA) is the most frequently diagnosed joint disorder worldwide with increasing prevalence and crucial impact on the quality of life of affected patients through chronic pain, decreasing mobility and invalidity. Although some risk factors, such as age, obesity and previous joint injury are well established, the exact pathogenesis of OA on a cellular and molecular level remains less understood. Today, the role of nitrosative and oxidative stress has not been investigated conclusively in the pathogenesis of OA yet. Therefore, the objective of this study was to identify biological substances for oxidative and nitrosative stress, which mirror the degenerative processes in an osteoarthritic joint. 69 patients suffering from a diagnosed knee pain participated in this study. Based on the orthopedic diagnosis, patients were classified into an osteoarthritis group (OAG, n=24) or in one of two control groups (meniscopathy, CG1, n=11; anterior cruciate ligament rupture, CG2, n=34). Independently from the study protocol, all patients underwent an invasive surgical intervention which was used to collect samples from the synovial membrane, synovial fluid and human serum. Synovial biopsies were analyzed histopathologically for synovitis (Krenn-Score) and immunohistochemically for detection of end products of oxidative (8-isoprostane F2α) and nitrosative (3-nitrotyrosine) stress. Additionally, the fluid samples were analyzed for 8-isoprostane F2α and 3-nitrotyrosine by competitive ELISA method. The analyzation of inflammation in synovial biopsies revealed a slight synovitis in all three investigated groups. Detectable concentrations of 3-nitrotyrosine were reported in all three investigated groups without showing any significant differences between the synovial biopsies, fluid or human serum. In contrast, significant increased concentrations of 8-isoprostane F2α were detected in OAG compared to both control groups. Furthermore, our data showed a significant correlation between the histopathological synovitis and oxidative stress in OAG (r=0.728, P<0.01). There were no significant differences between the concentrations of 8-isoprostane F2α in synovial fluid and human serum. The findings of the current study support the hypothesis that oxidative and nitrosative stress are components of the multi-factory pathophysiological formation of OA. It seems reasonable that an inflammatory process in the synovial membrane triggers the generation of oxidative and nitrosative acting substances which can lead to a further degradation of the articular cartilage. Based on correlations between the observed degree of inflammation and investigated biomarkers, especially 8-isoprostane F2α seems to be a novel candidate biomarker for OA. However, due to the finding that also both control groups showed increased concentrations of selected biomarkers, future studies have to validate the diagnostic potential of these biomarkers in OA and in related conditions of the knee joint.


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