Reactive Oxygen Species In Whole Blood Research Articles

Effect of Dipeptidyl-Peptidase 4 Inhibitors on Circulating Oxidative Stress Biomarkers in Patients with Type 2 Diabetes Mellitus.

Pre-clinical studies suggested potential cardiovascular benefits of dipeptidyl peptidase-4 inhibitors (DPP4i), however, clinical trials showed neither beneficial nor detrimental effects in patients with type 2 diabetes mellitus (T2DM). We examined the effects of DPP4i on several circulating oxidative stress markers in a cohort of 32 T2DM patients (21 males and 11 post-menopausal females), who were already on routine antidiabetic treatment. Propensity score matching was used to adjust demographic and clinical characteristics between patients who received and who did not receive DPP4i. Whole-blood reactive oxygen species (ROS), plasma advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), carbonyl residues, as well as ferric reducing ability of plasma (FRAP) and leukocyte DNA oxidative damage (Fpg sites), were evaluated. With the exception of Fpg sites, that showed a borderline increase in DPP4i users compared to non-users (p = 0.0507), none of the biomarkers measured was affected by DPP4i treatment. An inverse correlation between estimated glomerular filtration rate and AGEs (p < 0.0001) and Fpg sites (p < 0.05) was also observed. This study does not show any major effect of DPP4i on oxidative stress, assessed by several circulating biomarkers of oxidative damage, in propensity score-matched cohorts of T2DM patients.

Prokaryotic RNA Associated to Bacterial Viability Induces Polymorphonuclear Neutrophil Activation.

Polymorphonuclear neutrophils (PMN) are the first cellular line of antibacterial host defense. They sense pathogens through recognition of pathogen-associated molecular patterns (PAMPs) by innate pattern recognition receptors, such as Toll-like receptors (TLR). The aim of this study was to investigate whether PMN sense bacterial viability and explore which viability factor could be involved in this phenomenon. For this purpose, different functions were evaluated in isolated human PMN using live Escherichia coli (Ec) and heat-killed Ec (HK-Ec). We found that bacterial viability was indispensable to induce PMN activation, as measured by forward-scatter (FSC) increase, CD11b surface expression, chemotaxis, reactive oxygen species (ROS) generation and neutrophil extracellular trap (NET) formation. As uncapped non-polyadenylated prokaryotic mRNA has been recognized as a PAMP associated to bacterial viability by macrophages and dendritic cells, total prokaryotic RNA (pRNA) from live Ec was purified and used as a stimulus for PMN. pRNA triggered similar responses to those observed with live bacteria. No RNA could be isolated from HK-Ec, explaining the lack of effect of dead bacteria. Moreover, the supernatant of dead bacteria was able to induce PMN activation, and this was associated with the presence of pRNA in this supernatant, which is released in the killing process. The induction of bactericidal functions (ROS and NETosis) by pRNA were abolished when the supernatant of dead bacteria or isolated pRNA were treated with RNAse. Moreover, endocytosis was necessary for pRNA-induced ROS generation and NETosis, and priming was required for the induction of pRNA-induced ROS in whole blood. However, responses related to movement and degranulation (FSC increase, CD11b up-regulation, and chemotaxis) were still triggered when pRNA was digested with RNase, and were not dependent on pRNA endocytosis or PMN priming. In conclusion, our results indicate that PMN sense live bacteria through recognition of pRNA, and this sensing triggers potent bactericidal mechanisms.