Şahbettin Selek

Oxidative stress, inflammation and early cardiovascular damage in children with chronic renal failure

The relationship between inflammation, oxidant stress and cardiovascular damage in children with chronic renal failure (CRF) has not previously been investigated. The aim of this study was to investigate markers of oxidative stress, inflammation and early cardiovascular abnormalities. Therefore, erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities; blood glutathione (GSH) and serum malondialdehyde (MDA) levels; C-reactive protein (CRP) and proinflammatory cytokines (IL-6, TNF-α,); and left ventricular masses (LVM) and intima media thicknesses (IMT) were measured in children with CRF. A total of 29 children with CRF (19 nondialysis, 10 peritoneal dialysis) were included. The control group consisted of 25 healthy subjects. CRF children had significantly increased IL-6, TNF-α, CRP and MDA concentrations and decreased SOD, CAT and GSH levels compared with controls (P<0.05). Nondialysis and peritoneal dialysis subgroups had similar oxidative stress and inflammation biomarkers (P>0.05). Erythrocyte CAT was positively correlated with CRP, TNF-α, and IL2-R in the study group. Positive correlations were found between cytokine concentrations, CRP and urea/creatinine levels. Significantly increased LVM and IMT values were found in CRF children (P<0.05). In conclusion, increased oxidant stress and inflammation together with early cardiovascular damage were found in CRF children. Further studies with more patients are needed to verify these results.

The effects of dexmedetomidine on mesenteric arterial occlusion-associated gut ischemia and reperfusion-induced gut and kidney injury in rabbits.

OBJECTIVE We assessed the antioxidant activity of dexmedetomidine (Dex) administered during the ischemic period in a rabbit model of mesenteric ischemia/reperfusion (I/R) injury using biochemical and histopathological methods. METHODS A total of 24 male New Zealand white rabbits weighing between 2.5 and 3.0 kg were randomly divided into three groups: the sham group (Group S, n = 8), the I/R group (Group I/R, n = 8), and the I/R plus Dex treatment group (Group Dex, n = 8). In the I/R group, ischemia was achieved with 60 min of mesenteric occlusion. The sham group provided normal basal values. The rabbits in Group I/R were operated to achieve I/R. Group Dex received intravenous Dex 30 min after the commencement of reperfusion (10 μg/kg Dex was infused within 10 min, and then a maintenance dose of 10 μg/kg/h Dex was infused intravenously). For the measurement of tissue malondialdehyde, total antioxidant status, total oxidant status, lipid hydroperoxide levels, superoxide dismutase, catalase, and myeloperoxidase activity levels in the renal tissue samples of animals, the rabbits in each group were sacrificed 3 h after reperfusion. The histopathological examination scores were determined using the intestinal and renal tissues. RESULTS The mean malondialdehyde, total oxidant status, myeloperoxidase, and lipid hydroperoxide levels were significantly higher in Group I/R than in Groups S and Dex (P < 0.05). There also were significant decreases in the mean total antioxidant status, catalase, and superoxide dismutase activities in Group I/R compared with Groups S and Dex (P < 0.05). The histopathological examination scores of the intestinal and renal tissues were significantly higher in Group I/R compared with Groups S and Dex (P < 0.05). CONCLUSION Dex treatment may have biochemical and histopathological benefits by preventing I/R-related cellular damage of intestinal and renal tissues as shown in an experimental mesenteric ischemia model. The preference to use Dex for anesthesia during the mesenteric ischemia procedure may attenuate I/R injury in intestinal and renal tissues.

Oxidative Stress and Paraoxonase 1 Activity Predict Contrast-Induced Nephropathy in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Reactive oxygen species have been implicated in the pathogenesis of contrast-induced nephropathy (CIN). We investigated the relationship between CIN with paraoxonase 1 (PON-1) activity and oxidative stress markers (total antioxidant status [TAS], total oxidant status [TOS], and oxidative stress index [OSI]) in patients with anterior ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention; 289 consecutive patients with STEMI were prospectively included. The patients were divided into 2 groups: CIN (n = 69) and non-CIN (n = 220). Activity of PON-1 and TAS levels were significantly lower and OSI and TOS levels were significantly higher in patients with CIN compared to the non-CIN group (P < .05, for all). On multivariate logistic regression analysis, PON-1 activity and OSI as well as the amount of contrast medium and diabetes were independent predictors for CIN in patients with anterior STEMI. Activity of PON-1 and oxidative stress may play a role in the pathogenesis of CIN.

Paraoxonase-1 activity and oxidative stress in patients with anterior ST elevation myocardial infarction undergoing primary percutaneous coronary intervention with and without no-reflow.

BACKGROUND Reperfusion and ischemic injuries are pathogenetic mechanisms of no-reflow. Oxidative stress plays a critical role during ischemia as well as during the reperfusion phase following ST elevation myocardial infarction (STEMI). We sought to investigate the relationship between no-reflow with paraoxonase-1 (PON-1) activity and oxidative stress markers (total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), lipid hydro-peroxide (LOOH)) in patients with anterior STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS In this study, 319 consecutive anterior STEMI patients undergoing primary PCI were prospectively included (mean age 56.5 ± 12.5 years). The patients were divided into two groups as normal flow (n = 231) and no-reflow (n = 88) groups. Serum PON-1 activity was measured spectrophotometrically. TAC and TOS levels were determined by using an automated measurement method. LOOH levels were measured by ferrous oxidation with xylenol orange assay. RESULTS PON-1 activity and TAC levels were significantly lower and TOS, OSI and LOOH levels were significantly higher in patients with no-reflow compared to normal flow group (p < 0.05, for all). On multivariate logistic regression analysis, PON-1 activity (β = 0.976, 95% CI = 0.962-0.990, p = 0.001) and OSI (β = 1.094, 95% CI = 1.042-1.148, p < 0.001) as well as diabetes, infarction time, thrombus score and initial SYNTAX score were independently associated with no-reflow. CONCLUSION In patients with no-reflow compared with normal flow, oxidants are increased, while serum PON-1 activity and antioxidants are decreased. This result shows that increased oxidative stress has a role in the pathogenesis of no-reflow.

Paraoxonase-1 activity and oxidative status in patients with knee osteoarthritis and their relationship with radiological and clinical parameters

Abstract Background. The aim of this study was to investigate serum paraoxonase-1 (PON1) activity and oxidative/anti-oxidative status in knee osteoarthritis (OA), and evaluate their relationship using radiological and clinical parameters. Materials and methods. The study population comprised 127 patients with knee OA and 107 healthy volunteers. Patients with knee OA were divided into four subgroups according to the Kellgren–Lawrence (K&L) grading scale. In addition, each patient was clinically evaluated by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Serum PON1 activity was measured spectrophotometrically. Oxidative status was assessed by measuring serum lipid hydroperoxide (LOOH) and total oxidant status (TOS). Anti-oxidative status was assessed by measuring serum free sulfydryl groups (–SH = total thiol) and total antioxidant capacity (TAC). Oxidative stress index (OSI) was calculated. Lipid parameters were determined by routine laboratory methods. Results. Serum PON1 activity was significantly lower in the knee OA group compared to the control group (p < 0.001), whereas serum LOOH, TOS, and OSI levels of the knee OA group were significantly higher than those of the controls (p < 0.001 for all). However, TAC and –SH levels did not differ between the two groups (p > 0.05). The lowest and highest mean serum PON1 activities were detected in patients with grades 4 and 1, respectively (ANOVA p < 0.001). In multiple regression analysis, WOMAC score was independently associated with serum PON1 activity (β = –0.248, p = 0.027). Conclusions. Decreased serum PON1 activity and elevated LOOH, TOS, and OSI levels may be associated with knee OA, and serum PON1 activity may be a useful adjunctive indicator of the severity of knee OA for follow-up.

Oxidative Stress and Spontaneous Reperfusion of Infarct-Related Artery in Patients With ST-Segment Elevation Myocardial Infarction

In the pathogenesis of atherosclerosis, oxidative stress plays a major role in plaque instability, rupture, and erosion, which subsequently leads to thrombus formation and causes total infarct-related artery (IRA) occlusion. We investigated the relationship between spontaneous reperfusion (SR) of IRA and oxidative stress in patients with anterior ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. A total of 341 consecutive patients with anterior STEMI were prospectively included in the present study. Patients were divided into 2 groups according to their thrombolysis in myocardial infarction (TIMI) flow grade: SR group (66 patients, TIMI flow 3) and non-SR group (275 patients, TIMI flow 0-2). On multivariate logistic regression analysis, oxidative stress index (β = 0.868, 95% confidence interval [CI] = 0.806-0.934, P < .001), neutrophil to lymphocyte ratio, uric acid, mean platelet volume, Killip 2 to 4 class, and initial SYNTAX score were independently associated with SR. Oxidative stress as well as inflammation may play a pivotal role in the pathogenesis of SR in patients with STEMI.

Gamma glutamyl transferase activity is Independently associated with oxidative stress rather than SYNTAX score

Abstract Background. Gamma glutamyl transferase (GGT) is involved in the pathophysiologic process of coronary atherosclerosis. GGT activity plays a role in the catabolism of glutathione which is known as one of the major antioxidants. However, there is a lack of research on direct examination of relevance between serum GGT activity with systemic oxidative stress. Objectives. We aimed to investigate the relationship between GGT activity with systemic oxidative stress markers and the extent and complexity of coronary artery disease (CAD) assessed with SYNTAX score in stable CAD. Methods. Measurements were obtained from 359 patients with stable CAD (Mean age = 57.7 ± 10.1 years). The patients were divided into two groups according to the median GGT level (GGT < median group < 22 and GGT > median group ≥ 22). Angiography was performed and SYNTAX score was calculated in all patients. Oxidative stress markers (total oxidant status [TOS], total antioxidant capacity [TAC] and oxidative stress index [OSI]) were measured in all patients. Results. While SYNTAX score and oxidative stress markers such as TOS and OSI have been increased, TAC was decreased in GGT > median group compared with GGT < median group (p < 0.05, for all). GGT activity was independently associated with diabetes (β = 0.106, p = 0.015) and OSI (β = 0.556, p < 0.001) in multiple linear regression analysis. However, the independent association between GGT activity and SYNTAX score was not found in present study (β = 0.063, p = 0.238). Conclusion. In stable CAD, increased GGT activity within the normal range is associated with increased oxidative stress rather than increased extent and complexity of CAD.

Gamma Glutamyl Transferase Activity is Associated With Both Paraoxonase Activity and Aortic Stiffness in Hypertensive Patients

We aimed to investigate relationship between gamma glutamyl transferase (GGT) activity with paraoxonase 1 (PON1) activity and aortic stiffness (AS) parameters such as pulse wave velocity (PWV) and augmentation index (AIx).