8-hydroxy-2--deoxyguanosine and Sepsis

Reactive oxygen species (ROS) has a key role in the pathogenesis of sepsis. We wanted to evaluate ROS-associated lymphocyte necrosis and apoptosis.. A total of 51 patients were included in the study, 29 in the patient group and 22 in the control group. Blood samples were taken from patients in the patient group during severe sepsis or septic shock, then again once they had recovered. Oxidative DNA damage was evaluated by 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Peripheral blood lymphocytes from patients were evaluated with a microscope immediately. The rate of apoptosis and necrosis of lymphocytes were evaluated according to the number of cells in the peripheral.. The level of 8-OHdG increased with severe sepsis or septic shock. There were significant differences between the pre- and post-treatment values for apoptotic cell frequency (4.21±3.15 vs. 3.82±3.07, P<0.05) and necrotic cell frequency (4.75±3.61 vs. 4.09±3.37, P<0.05). Apoptosis and necrosis was increased during severe sepsis and septic shock, and apoptosis increase also continued after recovery, but necrosis decreased following disease recovery. CONCLUSıONS: In patients with severe sepsis or septic shock, apoptosis and necrosis were increased along with increased 8-OHdG level.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Apoptosis; Biomarkers; Deoxyguanosine; DNA Damage; Female; Humans; Lymphocytes; Male; Middle Aged; Necrosis; Reactive Oxygen Species; Sepsis; Shock, Septic

Simvastatin, which is primarily prescribed to lower cholesterol, may also mitigate lung injury caused by sepsis, although the mechanisms remain elusive. This study aimed to evaluate the protective effect of simvastatin on acute lung injury in rats with sepsis and to investigate possible mechanisms. Male Wistar rats were pretreated with simvastatin (0.2 μg/g) for 1 week before cecal ligation and puncture. Treatment with simvastatin demonstrated significant decreases in the concentration of protein, TNF-α, IL-1β, IL-6, and lipocalin 2, and the number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid in septic rats. In addition, simvastatin also reduced levels of Evans blue, malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and wet/dry lung weight ratios, and increased the activity of superoxide dismutase in lung tissue. Furthermore, expression levels of TLR4, NF-κB p65, and active caspase-3 proteins and Bax mRNA were also decreased by simvastatin. H&E staining showed that severe lung injury occurred in the sepsis group and that lung injury was reduced by treatment with simvastatin. In conclusion, simvastatin improved endothelial permeability and mitigated the inflammatory response of lung tissue, the oxidative stress response, and cell apoptosis by inhibiting the TLR4/NF-κB signaling pathway, thereby alleviating sepsis-induced acute lung injury in rats.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Bronchoalveolar Lavage Fluid; Caspase 3; Cytokines; Cytoprotection; Deoxyguanosine; Disease Models, Animal; Inflammation Mediators; Lipocalin-2; Lung; Male; Malondialdehyde; Oxidative Stress; Pulmonary Edema; Rats, Wistar; Sepsis; Signal Transduction; Simvastatin; Superoxide Dismutase; Toll-Like Receptor 4; Transcription Factor RelA

For appropriate sepsis care, prognostic laboratory markers are mandatory. The aim of our study was to evaluate the predictive value of serum actin, gelsolin and the recently defined actin/gelsolin ratio during sepsis by comparison it to classical clinical and inflammatory laboratory parameters.. We analyzed sera of severe septic (n=32) and SIRS (n=12) patients for 5days. Ophthalmologic patients (n=27) served as controls. Besides serum actin, gelsolin and actin/gelsolin ratios classical laboratory parameters (WBC count, serum procalcitonin, hsCRP) and clinical scores (APACHE II, SAPS II, SOFA), were also assessed.. Septic patients showed significantly decreased first-day gelsolin levels and increased actin/gelsolin ratios compared to SIRS patients (p<0.05), furthermore, non-survivors had significantly lower gelsolin levels compared to survivors (p<0.05). Non-survivors had 11.4-fold higher 2nd day actin/gelsolin ratios than survivors. Besides procalcitonin (PCT) and hsCRP, gelsolin and actin/gelsolin ratios also proved to be useful in discriminating SIRS from sepsis in the ICU (p<0.05). Gelsolin had similar prognostic value to PCT when assessing 7-day mortality and the predictive capacity of the first-day actin/gelsolin ratios was similar to that of APACHE II score regarding ICU mortality in severe sepsis.. Serum gelsolin and actin/gelsolin ratio might serve as efficient complementary prognostic markers in sepsis. However, for daily clinical usage, an automated laboratory assay of actin and gelsolin is still needed to be developed.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Actins; Aged; Deoxyguanosine; Female; Gelsolin; Glutathione; Homocysteine; Humans; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Sepsis

To determine whether urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an in vivo parameter of oxidative stress, is correlated with the outcome of critically septic patients.. Clinical outcome study in an adult medical intensive care unit (ICU).. 85 consecutive septic patients (59 men, 26 women).. Patient characteristics and the clinical course were examined. Urinary 8-OHdG was analyzed using isotope-dilution liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU mortality was 25.9% (22/85) and hospital mortality 38.8% (33/85). Survivors' APACHEII scores on days 1 and 3 and the difference between them differed significantly from those of nonsurvivors (day 1, 21.0+/-7.1 vs. 25.9+/-8.0; day 3, 15.0+/-5.8 vs. 23.2+/-8.3; difference, 6.0+/-5.5 vs. 1.7+/-6.6). Urinary 8-OHdG was significantly lower in survivors than in nonsurvivors on day 1 (1.8+/-2.4 vs. 3.0+/-2.4). The area under receiver operating characteristic curve analysis for the association between day 1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon discharge from hospital revealed similar results.. This is a preliminary study. Excretion of urinary 8-OHdG, as measured using isotope-dilution LC/MS/MS, and the APACHE II score were correlated with the outcome of critically septic patients in medical ICU.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; APACHE; Biomarkers; Chromatography, Liquid; Critical Illness; Deoxyguanosine; Female; Humans; Male; Oxidative Stress; Radioisotope Dilution Technique; Sepsis; Tandem Mass Spectrometry