Ezel Uslu

Protective Effect of the Nuclear Factor Kappa B Inhibitor Pyrrolidine Dithiocarbamate in Lung Injury in Rats with Streptozotocin-Induced Diabetes

Background: Diabetes mellitus (DM) causes debilitating complications and, as a result, diabetics frequently require intensive care. Although lungs are not thought to be affected primarily by DM, an increasing number of studies indicate physiological and structural abnormalities in diabetic lungs. Objectives: Pyrrolidine dithiocarbamate (PDTC) is a metal chelator and a potent inhibitor of NF-ĸB. Keeping in mind that NF-ĸB activation may be crucial in end-organ injury due to DM, we studied the role of PDTC on the inhibition of NF-ĸB activation and its effects on possible lung injury in rats with streptozotocin-induced DM. Methods: 36 Sprague-Dawley rats were allocated into 4 groups: diabetes, diabetes + PDTC, control and control + PDTC. At the end of 10 weeks, rats were sacrificed and their lungs were taken for histopathological and immunohistochemical evaluation [for NF-ĸB (p65) and endothelial nitric oxide (eNOS) immunoreactivities]. Protein carbonyl content (PCC), superoxide dismutase (SOD) and reduced glutathione (GSH) activities were measured. Results: Histopathologically, basal membranes were thickened and there was intense inflammatory reaction in diabetic lungs. However, the PDTC group, in which there were poor positive expressions of eNOS and p65 activity compared to diabetes group, revealed fewer inflammatory changes. PCC levels in diabetic lungs were higher, but SOD and GSH activities were lower. However, measurements of these parameters in the PDTC group and controls gave similar results. Conclusion: Lungs are exposed to changes induced by oxidative stress in diabetes through NF-ĸB activation and PDTC seems to be useful to prevent diabetic lung injury.

Redox Homeostasis of Albumin in Relation to Alpha-Lipoic Acid and Dihydrolipoic Acid

Albumin represents the predominant circulating antioxidant agent in plasma exposed to continuous oxidative stress and a change in serum albumin structure accounts for its antioxidant properties. Alterations in the redox status of albumin may result in impairments of its biological properties. Alpha-lipoic acid (LA), a naturally occurring thiol compound found in virtually all species, is a potent antioxidant with high efficacy which is also involved in the chelation of metal ions, regeneration of antioxidants, and repair of oxidatively damaged proteins. In human body LA is rapidly reduced to dihydrolipoic acid (DHLA) after intake into the cell. Both, LA and DHLA are amphipathic molecules which act as antioxidants both in hydrophilic and lipophilic environments. The present study aimed to investigate the antioxidant/pro-oxidant effects of LA and DHLA due to their concentrations in metal-catalyzed protein oxidation (MCO) of human serum albumin (HSA). Progressive oxidative modification of albumin was found in MCO system by an increased content of protein hydroperoxides (POOH), protein carbonyl groups (PCO) which is the formers major breakdown product, and other protein oxidation markers such as advanced oxidized protein products (AOPP) and protein thiol groups (P-SH). The possible antioxidant protective effects of LA and DHLA were observed with 25 microM and 50 microM; DHLA being more influential. Protein oxidation parameters were found to be lower and P-SH levels seemed higher. However, prooxidant effects of both LA and DHLA came on the scene with increased concentrations of 75 microM and 100 microM where the latter seemed the most hazardous with contradicted results. It is clear that the loss of biological activity of human serum albumin by MCO system appears of medical relevance and if LA exerts similar effects seen in the present study, it is possible that cellular prooxidant activity can also result consuming this unique antioxidant in certain doses.

Effects of recombinant human growth hormone and nandrolone phenylpropionate on the healing of ischemie colon anastomosis in rats

PurposeRecombinant human growth hormone and nandrolone phenylpropionate are two different anabolic agents. This study was designed to investigate the effects of these anabolic agents on the healing of ischemie colon anastomosis in rats. METHODS: Seventy adult male Wistar rats were divided into five groups (n = 14). Group I was the sham laparotomy group. In the other groups, surgical procedures consisting of transsection and anastomosis were made at a distance 3 cm from the peritoneal reflection. Group II was the nonischemic control group. Ischemie colon model was produced in the remaining groups. Group III was the untreated control group. Groups IV and V received recombinant human growth hormone and nandrolone phenylpropionate, respectively. Bursting pressure and hydroxyproline levels were measured on the third and seventh postoperative days to evaluate anastomotic healing. RESULTS: Recombinant human growth hormone increased both collagen deposition and bursting pressure significantly at postoperative Days 3 and 7 compared with the sham and untreated control groups (P < 0.005). When compared with the untreated control, nandrolone phenylpropionate significantly increased collagen deposition at postoperative Days 3 and 7 (P < 0.005) and bursting pressure only at postoperative Day 3 (P < 0.005). CONCLUSIONS: Recombinant human growth hormone has more favorable therapeutic effects on the healing of ischemie colonie anastomoses than nandrolone phenylpropionate. Recombinant human growth hormone also improves healing of nonischemic colonie anastomosis.

Increased Protein Oxidation and Loss of Protein-Bound Sialic Acid in Hepatic Tissues of D-galactose Induced Aged Rats

A redox basis of the increased oxidative protein damage and free radical-mediated desialylation have not been fully elucidated in aging. It is well known that the incidence of several liver diseases increase with age. This original research focuses on protein oxidation mechanisms and protein-bound sialic acid levels in liver tissue of the mimetic aging rats. Injection of D-galactose (60 mg/kg/day) for six weeks to male Sprague-Dawley rats (20-week-old) used to establish mimetic aging model. We investigated the tissue levels of various protein oxidation markers such as protein carbonyl groups, suitable advanced oxidation protein products and protein thiol groups. Our study also covered protein-bound sialic acid in liver tissue of D-galactose-induced aging rats. PCO (Protein Carbonyl Groups), P-OOH (Protein Hydroperoxides) and AOPP (Advanced Oxidation Protein Products) levels in aging rats were significantly higher compared to young control groups. On the other hand, P-SH (Protein Thiol Groups) levels were not found to be different between two groups. SA (Sialic Acid) levels in D-galactose-induced aging rats were significantly lower compared to control groups. Our results demonstrated greater susceptibility to hepatic oxidative protein damage and desialylation of hepatocellular proteins in Dgalactose- induced aging rats. These molecular mechanisms may be operative in the many age-related liver diseases, which are pertinent to increased oxidative stress and altered redox homeostasis.

Effect of tempol on redox homeostasis and stress tolerance in mimetically aged Drosophila

We aimed to test our hypothesis that scavenging reactive oxygen species (ROS) with tempol, a membrane permeable antioxidant, affects the type and magnitude of oxidative damage and stress tolerance through mimetic aging process in Drosophila. Drosophila colonies were randomly divided into three groups: (1) no D-galactose, no tempol; (2) D-galactose without tempol; (3) D-galactose, but with tempol. Mimetic aging was induced by d-galactose administration. The tempol-administered flies received tempol at the concentration of 0.2% in addition to d-galactose. Thiobarbituric acid reacting substance (TBARS) concentrations, advanced oxidation protein products (AOPPs), Cu,Zn-superoxide dismutase (Cu,Zn-SOD), sialic acid (SA) were determined. Additionally, stress tolerances were tested. Mimetically aged group without tempol led to a significant decrease in tolerance to heat, cold, and starvation (P < 0.05), but tempol was used for these parameters. The Cu,Zn-SOD activity and SA concentrations were lower in both mimetically aged and tempol-administered Drosophila groups compared to control (P < 0.05), whereas there were no significantly difference between mimetically aged and tempol-administered groups. Mimetically aged group without tempol led to a significant increase in tissue TBARS and AOPPs concentrations (P < 0.05). Coadministration of tempol could prevent these alterations. Scavenging ROS using tempol also restores redox homeostasis in mimetically aged group. Tempol partly restores age-related oxidative injury and increases stress tolerance.

The effects of ageing on brain tissue sialic acid contents following cold trauma

Summary.Background. There is a prominent difference between the responses of young and aged patients to brain injury in the clinical setting, but the exact cause of this condition is not well known.Methods. Young (3–4 months) and aged (36–40 months) Wistar albino male rats were used as subjects, and they were divided into four groups: young and aged study groups, and young and aged control groups. In all groups, craniectomies were performed over the left hemispheres, and in the study groups, cold injuries were inflicted. Brain tissue sialic acid contents were determined in all groups.Findings. Brain tissue sialic acid content was higher in aged control rats than young control ones, but the difference was not statistically significant. Tissue sialic acid content was significantly increased in young rats after trauma. On the contrary, it was significantly decreased in aged rats after trauma.Interpretation. In young rats, brain tissue sialic acid content was significantly increased 24 hours after cold injury unlike in the aged ones. This may be a finding related to decreased regeneration capability of aged brain.

Gender and chronological age affect erythrocyte membrane oxidative indices in citrate phosphate dextrose adenine-formula 1 (CPDA-1) blood bank storage condition.

It is well known that in vitro storage lesions lead to membrane dysfunction and decreased number of functional erythrocytes. As erythrocytes get older, in storage media as well as in peripheral circulation, they undergo a variety of biochemical changes. In our study, the erythrocytes with different age groups in citrate phosphate dextrose adenine-formula 1 (CPDA-1) storage solution were used in order to investigate the possible effect of gender factor on oxidative damage. Oxidative damage biomarkers in erythrocyte membranes such as ferric reducing antioxidant power, pro-oxidant-antioxidant balance, protein-bound advance glycation end products, and sialic acid were analyzed. Current study reveals that change in membrane redox status during blood-bank storage condition also depends on both gender depended homeostatic factors and the presence of CPDA-1. During the storage period in CPDA-1, erythrocytes from the male donors are mostly affected by free radical-mediated oxidative stress but erythrocytes obtained from females are severely affected by glyoxidative stress.

The influence of hemodialysis on serum sialic acid levels in chronic renal failure

AbstractBackground. It has been observed that there is an increase in serum sialic acid level in chronic renal diseases and endstage renal failure requiring hemodialysis, and the hemodialysis procedure causes increased cytokine production. Thus, it is expected that hemodialysis causes increases in the serum levels of acute phase reactants and sialic acid. Nevertheless, the changes in serum sialic acid level in hemodialysis have not been examined sufficiently. In our study, we examined the effect of hemodialysis on serum sialic acid level. Methods. A total of 54 patients on hemodialysis therapy for chronic renal failure (32 men; 22 women) were examined. The patients were evaluated in four groups according to their age, sex, duration of hemodialysis, and whether they were diabetic. Serum sialic acid levels before and after hemodialysis, done with a hemophane membrane, were measured by the thiobarbituric acid method described by Warren. Results. The serum sialic acid levels of chronic renal failure patients requiring hemodialysis were increased with respect to the healthy control group, independent of age, duration of therapy, and whether there was accompanying diabetes. Hemodialysis did not provide clearance of sialic acid; to the contrary, it caused an insignificant increase in serum sialic acid levels. Conclusions. In chronic renal failure, the improved serum sialic acid level probably reaches a definite value, and this value is not affected by factors such as diabetes, age, or sex. Serum sialic acid level is minimally influenced by hemodialysis performed with a hemophane membrane.

Mechanical bowel preparation with different solutions in rats with selective left colonic ischemia and reperfusion injury

BACKGROUND The aim of this study was to evaluate the effects of preoperative mechanical bowel preparation (MBP) on colonic ischemia/reperfusion (I/R) injury. METHODS Seventy adult male Sprague-Dawley rats were divided randomly into 7 equal groups of 10 rats each. Groups were assigned as follows: group I = sham surgery; group II = I/R of left colon (control group); group III = intravenous heparin and metronidazole followed by I/R of the left colon; groups IV through VII = before I/R of the left colon, heparin and metronidazole and MBP were performed with sodium chloride (NaCl), Na phosphate, polyethylene glycol, and mannitol, respectively. Histopathologic and biochemical parameters were evaluated. RESULTS According to the histopathologic changes, the groups least affected by I/R injury were groups V and VII. Catalase activity was significantly higher in groups V and VII, and copper-zinc superoxide dismutase activity was significantly higher in group VII compared with the control group (P <.002). CONCLUSIONS MBP with sodium phosphate and mannitol appears to be more protective against I/R injury.