Necmiye Canacankatan

Oxidant-antioxidant balance in patients with COPD.

The goal of this study was to evaluate the role of oxidant–antioxidant balance in the pathogenesis of COPD. We included 30 healthy nonsmokers [24 male, 6 female; mean age (yr) ± SD: 62.4 ± 9.3], 30 healthy smokers [27 male, 3 female; mean age (yr) ± SD: 58.7 ± 6.0], 71 patients with stable COPD [68 male, 3 female; mean age (yr) ± SD: 63.5 ± 7.9], and 31 patients with COPD exacerbation [30 male, 1 female; mean age (yr) ± SD: 64.2 ± 7.3]. In all study groups the peripheral venous blood samples were taken for plasma malonyldialdehyde (MDA), a parameter of lipid peroxidation caused by the oxidants, and erythrocyte superoxide dismutase (SOD), an antioxidant enzyme. The mean plasma MDA level was higher in healthy smokers and in patients with COPD than in healthy nonsmokers (p < 0.05), and erythrocyte SOD enzyme activity in patients with COPD exacerbation (1048.2 ± 226.5 Ug/Hb) was significantly higher than in healthy nonsmokers (947.9 ± 198.0 Ug/Hb) (p < 0.05). Although mean erythrocyte SOD enzyme activity in healthy smokers and patients with stable COPD was higher than in healthy nonsmokers, the difference was not statistically significant. We found that healthy smokers and stable and exacerbated COPD patients had an impairment in oxidant–antioxidant balance. We suggested that new therapeutic interventions, which may repair the impaired oxidant-antioxidant balance in COPD, are needed to prevent the development of COPD.

The oxidant-antioxidant balance in mild asthmatic patients.

We investigated the oxidant-antioxidant balance and the effect of inhaled corticosteroids on this balance in mild stable asthmatics. Included in the study were 30 mild asthmatic patients (11 male, 19 female, mean age (year) ± SD: 35.1 ± 9.7) and 26 healthy adults (7 male, 19 female, mean age (year) ± SD: 40.8 ± 13.3). In all study groups, the peripheral venous blood samples were taken for plasma malonyldialdehyde (MDA), a parameter of lipid peroxidation caused by the oxidants, and erythrocyte superoxide dismutase (SOD), an antioxidant enzyme. The mean plasma MDA level was lower in the asthmatic group (5.7 ± 1.2 nmol/ml) than in the healthy group (6.3 ± 1.7 nmol/ml); and the mean erythrocyte SOD level was higher in asthmatic group (1086.4 ± 247.4 U/gHb) than in the healthy group (1028.0 ± 230.0 U/gHb). However, there were no significant differences in measurements of both plasma MDA levels and erythrocyte SOD enzyme activities between the groups (respectively, p = 0.1 and p = 0.4). When asthmatic patients were divided into subgroups as “inhaled steroid user” and “no inhaled steroid user”, no significant differences were observed in the measurements of either plasma MDA level or erythrocyte SOD enzyme activity between the mentioned subgroups. According to the results of our study, we can say that oxidant-antioxidant balance is not significantly affected in mild asthmatics or measurement of plasma level of MDA and erythrocyte SOD enzyme activity is not sensitive to the oxidant-antioxidant balance in mild asthmatics.

The Effects of Methyl Methacrylate on Nasal Cavity, Lung, and Antioxidant System (An Experimental Inhalation Study)

Methyl methacrylate (MMA) is a monomer, commonly used in neurosurgery, orthopedic surgery, and in dental clinics. The adverse effects of this monomer are well described in the literature. This study was designed to evaluate the effects of MMA on nasal cavity, lung, and antioxidant status. For this purpose, two experimental groups of rats were exposed to MMA (at 1000 ppm, 6 h/day, 5 days/week for 4 weeks) by inhalation under poor (group A, n = 12) and normal ventilation (group B, n = 11) conditions. A control group (group C, n = 10) received normal air. Degeneration of olfactory epithelium, bronchopneumonia , interstitial pneumonia, hemorrhage, atelectasis, edema, emphysema, and bronchial epithelial hyperplasia were observed in groups A and B. Emphysema was the most common lesion. Bronchopneumoni a with abscesses was only observed in group A. Glutathione levels were signifi cantly decreased and malondialdehyde levels were signifi cantly increased in group A. No signifi cant difference was observed in superoxide dismutase levels between the groups. The data presented indicate that before using MMA, adequate protection systems should be in place to prevent occupationally related MMA respiratory-tract injuries.

effects of L-carnitine and niacin supplied by drinking water on fattening performance, carcass quality and plasma L-carnitine concentration of broiler chicks

The present study was initiated to determine whether dietary supplemental L-carnitine and niacin affect growth performance, carcass yield, abdominal fat and plasma L-carnitine concentration of broiler chicks. One-day-old broiler chicks (COB500) were used in the experiment. A two by two factorial arrangement was employed with two levels (0 and 50 mg/l) of supplemental L-carnitine and two levels (0 or 50 mg/l) of supplemental niacin in drinking water as main effects. Body weight gain was significantly improved by L-carnitine, or L-carnitine + niacin supplementation during the first 3 weeks. However, supplemental L-carnitine and niacin did not change body weight gain during the last 3 weeks of the experimental period. Supplemental L-carnitine significantly improved feed intake during the first 3 weeks. Supplemental L-carnitine or niacin did not influence carcass weight, carcass yield and abdominal fat weight. L-carnitine content in the plasma was significantly higher in the groups receiving supplemental L-carnitine and L-carnitine + niacin. It is concluded that dietary supplemental L-carnitine or L-carnitine + niacin could have positive effects on body weight gain and feed intake during the early stages of growing. However, supplemental L-carnitine or L-carnitine + niacin were not of benefit regarding the complete growth period.

The effects of indomethacin on caspases, glutathione level and lipid peroxidation in the newborn rats with hypoxic-ischemic cerebral injury

Activation of phospholipase A(2), degradation of membrane phospholipids resulting in tissue accumulation of arachidonic acid, and the activation of cyclooxygenase that leads to the formation of prostaglandin and free radicals may occur after hypoxic-ischemic damage. The aim of this study was to investigate the effects of indomethacin, a nonselective cyclooxygenase inhibitor, on caspase activity, glutathione levels and lipid peroxidation in newborn rats with hypoxic-ischemic encephalopathy. The effects of indomethacin were evaluated by measuring caspase-3 and caspase-8 activities and glutathione levels. Lipid peroxidation was evaluated by measuring concentrations of malondialdehyde in rat brains. Seven-day-old rat pups with the Levine-Rice model of hypoxic-ischemic cerebral injury were randomly divided into three study groups. In the indomethacin-treated group, rats were administered three doses of indomethacin, at a dose of 2 mg/kg every 12 h. Sham and the hypoxic-ischemic group of rats were given physiologic saline. The sham group underwent all surgical procedures except for arterial ligation. After 72 hours, the rats were decapitated and brain tissues were evaluated. Caspase-3 and caspase-8 activities and glutathione and malondialdehyde levels were evaluated in all groups. There was an obvious decrease in caspase-3 and caspase-8 activities and depleted glutathione levels were reversed in the indomethacin-treated group compared to the hypoxic-ischemia group (p<0.001). As indomethacin was unable to prevent lipid peroxidation, malondialdehyde concentrations increased to ischemia-induced levels. In conclusion, indomethacin administration after hypoxic-ischemic encephalopathy injury has a neuroprotective effect since it inhibits caspase activity and reverses the depletion of glutathione. However, it also aggravates lipid peroxidation-induced ischemia.

Contribution of RhoA/Rho-kinase/MEK1/ERK1/2/iNOS pathway to ischemia/reperfusion-induced oxidative/nitrosative stress and inflammation leading to distant and target organ injury in rats.

The small G protein RhoA and its downstream effector Rho-kinase play an important role in various physiopathological processes including ischemia/reperfusion (I/R) injury. Reactive oxygen and nitrogen species produced by iNOS and NADPH oxidase are important mediators of inflammation and organ injury following an initial localized I/R event. The aim of this study was to determine whether RhoA/Rho-kinase signaling pathway increases the expression and activity of MEK1, ERK1/2, iNOS, gp91(phox), and p47(phox), and peroxynitrite formation which result in oxidative/nitrosative stress and inflammation leading to hindlimb I/R-induced injury in kidney as a distant organ and gastrocnemius muscle as a target organ. I/R-induced distant and target organ injury was performed by using the rat hindlimb tourniquet model. I/R caused an increase in the expression and/or activity of RhoA, MEK1, ERK1/2, iNOS, gp91(phox), p47(phox), and 3-nitrotyrosine and nitrotyrosine levels in the tissues. Although Rho-kinase activity was increased by I/R in the kidney, its activity was decreased in the muscle. Serum and tissue MDA levels and MPO activity were increased following I/R. I/R also caused an increase in SOD and catalase activities associated with decreased GSH levels in the tissues. Y-27632, a selective Rho-kinase inhibitor, (100µg/kg, i.p.; 1h before reperfusion) prevented the I/R-induced changes except Rho-kinase activity in the muscle. These results suggest that activation of RhoA/Rho-kinase/MEK1/ERK1/2/iNOS pathway associated with oxidative/nitrosative stress and inflammation contributes to hindlimb I/R-induced distant organ injury in rats. It also seems that hindlimb I/R induces target organ injury via upregulation of RhoA/MEK1/ERK1/2/iNOS pathway associated with decreased Rho-kinase activity.

Affirmative Effects of Iloprost on Apoptosis during Ischemia-Reperfusion Injury in Kidney as a Distant Organ

Abstract Objective: Apoptosis and its regulatory mechanisms take part in renal ischemia–reperfusion (I/R) injury which can result in acute renal failure and the inhibition of the caspase is considered as a new therapeutic strategy. In this context, we investigated the antiapoptotic and cytoprotective effects of iloprost, a prostacyclin analog, in kidney as a distant organ. Methods: Wistar albino rats were randomized into five groups (n = 12 in each) as sham, ischemia, I/R, iloprost (10 μg kg−1), and I/R + iloprost (10 μg kg−1). A 4 h reperfusion procedure was carried out after 4 h of ischemia. Caspase-8 was evaluated for death receptor-induced pathways, whereas caspase-9 was evaluated for mitochondria-dependent pathways and caspase-3 was investigated for overall apoptosis. Superoxide dismutase (SOD) enzyme activity and nitrite content as an indicator of nitric oxide (NO) production were also analyzed in kidney tissues. Results: Caspases-3, -8, and -9 were all significantly elevated in both ischemia and I/R groups compared to the sham group; however, treatment with iloprost reduced caspases-3, -8, and -9. SOD enzyme activity was attenuated by iloprost when compared to ischemic rats. The different effects of NO were found which change according to the present situation in ischemia, I/R, and treatment with iloprost. Conclusions: These findings suggested that iloprost prevents apoptosis in both receptor-induced and mitochondria-dependent pathways in renal I/R injury and it may be considered as a cytoprotective agent for apoptosis. Understanding the efficiency of iloprost on the pathways for cell death may lead to an opportunity in the therapeutic approach for renal I/R injury.

Effects of intravitreal bevacizumab in repeated doses: an experimental study.

Purpose: To evaluate the effects of repeated 1.25-mg intravitreal bevacizumab injections on cornea and uveoretinal tissues using histologic and biochemical analyses. Methods: Twenty-four New Zealand albino rabbits were used. Twelve rabbits received an injection of bevacizumab in their right eyes three times with an interval of 25 days (Group 1); their contralateral eyes served as controls (Group 2). Six rabbits had an injection of vehicle in both eyes (Group 3), with the same regimen as bevacizumab, and six rabbits’ eyes were used as a sham group (Group 4). Enucleated eyes were used for histologic and biochemical analyses, which included the activities of caspase 3 and 8 enzymes, glutathione content, catalase activity, and malondialdehyde content. Results: No inflammation in aqueous humor and no sign of corneal or uveoretinal toxicity was found in bevacizumab-injected eyes. The difference of activity of corneal caspase 8 enzyme between Groups 1 and 2 and between Groups 1 and 4 was statistically significant (P < 0.05). In the uveoretinal tissue, in Group 1, the activities of caspase 3 and 8 enzymes were the lowest, and uveoretinal malondialdehyde content was also significantly lower than Group 4. Conclusion: A repeated dose of intravitreal bevacizumab injection did not cause a toxic effect on cornea and uveoretinal tissue. Biochemically, it also did not cause any apoptosis, oxidative reaction, or lipid peroxidation. Instead, bevacizumab injection caused a considerable decrease in the apoptotic enzyme activities and lipid peroxidation in the uveoretinal tissue. Further studies are needed to be conducted for possible detrimental side effects and apoptotic and oxidative effects of repeated bevacizumab injections on both the injected and the contralateral eyes.

Intravitreal bevacizumab effects on VEGF levels in distant organs: an experimental study

Abstract Purpose: The aim of this study was to determine the effects of single-dose intravitreal bevacizumab on the levels of vascular endothelial growth factor (VEGF) in serum and distant organs. Methods: Adult New Zealand albino rabbits (n = 40) were divided into experimental and control groups. Experimental rabbits received a single 0.05 ml intravitreal injection of 1.25 mg bevacizumab (Avastin) into the right eye, and control rabbits (n = 8) received no injection. Following injection, group 1 rabbits (n = 8) were sacrificed on day 1, group 2 rabbits (n = 8) on day 7, group 3 rabbits (n = 8) on day 14, and group 4 rabbits (n = 8) on day 28; control rabbits were sacrificed on day 28. After sacrifice, samples of brain, heart, liver, kidney and blood were collected. Levels of VEGF in serum and tissue were measured using enzyme-linked immunosorbent assay. The presence of bevacizumab was evaluated by immunofluorescence staining in tissues. Results: Positive bevacizumab immunoreactivity was observed in brain, heart and kidney. Serum VEGF levels significantly decreased in groups 3 and 4 compared with controls (p < 0.05). Liver VEGF levels significantly decreased in group 3 compared with controls (p < 0.05). Conclusions: Intravitreal bevacizumab not only may escape from the blood-retinal barrier and enter the general circulation, but also may be disseminated to distant organs. Our study demonstrates that a single dose of intravitreally injected bevacizumab decreases VEGF levels in serum and liver.

The effect of different treatment modalities on oxidative stress in COPD

IntroductionOxidant/antioxidant interactions are known to be important processes in the pathogenesis of chronic obstructive pulmonary disease (COPD). We aimed to evaluate the effects of corticosteroids (CS), and Nacetylcysteine (NAC) on plasma oxidant/antioxidant levels in patients with COPD.MethodsThis study utilised a single-blind, randomised, placebo-controlled, parallel-group methodology. We enrolled 58 patients with stable COPD and 30 healthy controls with similar demographic profiles. The patients with COPD were randomly divided into three treatment groups. Group 1 received basal treatment (regular ipratropium bromide and beta-2 agonist as needed), placebo CS and placebo NAC. In addition to basal treatment, group 2 received oral CS (methylprednisolone 40 mg/day) and placebo NAC. Group 3 received basal treatment plus NAC (600 mg/day) and placebo CS. Each group received treatment for 15 days. We measured plasma malondialdehyde (MDA) and superoxide dismutase (SOD) at the start and the end of study.ResultsPost-treatment plasma MDA levels were significantly lowered only in group 2 (P=0.004). No significant differences were found with respect to erythrocyte SOD levels.ConclusionThis study demonstrates that oral CS, by aiding the oxidant/antioxidant system, may offer a new therapeutic option in COPD treatment.