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Öğe Altered diurnal variation of nitric oxide production in patients with panic disorder(Tohoku Univ Medical Press, 2004) Kaya, B; Ünal, S; Karabulut, AB; Türköz, YThe aim of this prospective study was to investigate the diurnal change in serum nitric oxide (NO) levels in active and remission phases of patients with panic disorder. This study included 15 patients fulfilling the criteria for panic disorder of Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition and 15 healthy controls matched for age and sex. All patients were receiving a selective serotonin reuptake inhibitor at therapeutic doses. The serum nitrite and nitrate levels of subjects were determined at 10: 00 a.m. after overnight fasting and at 3: 00 p.m. 2 hours after lunch. NO levels of all patients measured in the morning were significantly higher than those of controls. The patients were also divided into active and remission groups according to clinical status and Panic Agoraphobia Scale's cut-off point. There were no statistically significant differences in serum nitrite and nitrate levels of the active group between the 10:00 a.m. and 3:00 p.m. measurements. In contrast, statistically significant differences were found in the serum levels of nitrite (p<0.05) and nitrate (p<0.05) in the remission group. Notably, the afternoon nitrite and nitrate levels of the remission group were higher than those of the morning levels as seen in control subjects. Thus, diurnal variation of NO production is altered in patients with panic disorder but is resumed in the remission phase. The present study suggests that serum NO levels are a good marker for evaluation of panic disorder. (C) 2004 Tohoku University Medical Press.Öğe Association between cytokines in induced sputum and severity of chronic obstructive pulmonary disease(W B Saunders Co Ltd, 2006) Hacievliyagil, SS; Gunen, H; Mutlu, LC; Karabulut, AB; Temel, ICytokines are known to be increased in induced sputum in chronic obstructive pulmonary disease (COPD). In this study, the relationship between the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-alpha (TNF-alpha) in induced sputum of patients with exacerbation of COPD, and the severity of the disease, pulmonary function tests (PFT), arterial blood gases (ABG) were studied. Twenty-four patients with exacerbation of COPD were included in the study. The patients were grouped according to their PFT into two as: Group 1 (FEV, below 50% of the predicted value, severe-very severe COPD, n = 12) and, Group 2 (FEV, above 50% of the predicted value, mild-moderate COPD, n = 12). The levels of IL-6, IL-8 and TNF-alpha in induced sputum of the subjects were measured. The mean levels of IL-6, IL-8 and TNF-alpha in induced sputum were found to be higher in Group 1 (severe-very severe COPD) than in Group 2 (mild-moderate COPD). The differences in IL-6 and IL-8 levels between groups were statistically significant (P < 0.05). A significant correlation was observed between the IL-6 value and FEV1 (r = -0.435, P = 0.034), FEV1/FVC (r = -0.446, P = 0.029), PaO2 (r = -0.711, P = 0.000), SaO(2) (r = -0.444, P = 0.030) and disease duration (r = 0.427, P = 0.037), respectively. Also, the level of IL-8 in induced sputum was inversely correlated with FEV1 (r = -0.562, P = 0.004), PaO2 (r = -0.540, P = 0.006) and SaO(2) (r = -0.435, P = 0.034). However, all three cytokines were positively correlated with the smoking load (r = 0.653, P = 0.001; r = 0.439, P = 0.032; r = 0.649, P = 0.001). We conclude, therefore, that in exacerbated COPD cases with greater degrees of obstruction of the airways have higher levels of cytokines in induced sputum. This can be interpreted to mean that these cytokines are related to the clinical parameters like the ABG and PFT and seem to be the determinant of the severity of the disease. (c) 2005 Elsevier Ltd. All rights reserved.Öğe Chronic effects of fluoride in Tuj sheep on serum levels of total protein, albumin, uric acid, and nitric oxide and activities of lactate dehydrogenase and leucine aminopeptidase(Int Soc Fluoride Research, 2005) Cenesiz, S; Ozcan, A; Kaya, N; Baysu, N; Karabulut, ABTwenty healthy yearling Tuj ewe-lambs with a mean body weight of 31 2 kg were divided into two equal groups. Each group of ten sheep was provided with hay and water ad libitum throughout the study. The water for the control group contained 0.49 mg F/L, whereas the water for the experimental group contained 13.8 mg F/L, equivalent for the latter group to an intake of ca. 1.8 mg F/kg bw/day. By the 12(th) week the urinary fluoride concentration in the experimental group had increased from 0.9 ppm at the start to 1.78 ppm, and by the 24(th) week it reached 8 ppm, at which point various serum determinations were made and the study was terminated. In the experimental vs. the control groups the results were as follows: total protein 7.41 +/- 0.03 vs. 7.67 +/- 0.07 g/dL (p<0.01), albumin 3.97 +/- 0.36 vs. 4.72 +/- 0.28 g/dL, nitric oxide 49.90 +/- 3.1 vs. 35.75 +/- 2.7 mu mol/L (p < 0.01), uric acid 0.49 +/- 0.03 vs. 0.29 +/- 0.02 mg/dL (p < 0.001), lactate dehydrogenase (LDH) 676.7 +/- 21 vs. 518 +/- 35 U/L (p < 0.01), and leucine aminopeptidase (LAP) 7.28 +/- 0.5 vs. 6.18 +/- 0.53 U/L. Changes in the albumin level and the LAP activity were not statistically significant. During and at the end of the study the urine fluoride concentration of the control group was unchanged.Öğe A comparative study of superoxide dismutase, catalase, and glutathione peroxidase activities and nitrate levels in vitiligo patients(Wiley, 2005) Hazneci, E; Karabulut, AB; Öztürk, Ç; Batçioglu, K; Dogan, G; Karaca, S; Esrefoglu, MBackground Several groups have shown the involvement of oxidative stress in the pathophysiology of vitiligo. Methods In this study, we examined the erythrocyte and plasma activities of glutathione peroxidase and Cu/Zn superoxide dismutase, plasma nitrite/nitrate levels, and erythrocyte catalase activity in 23 vitiligo patients and 25 controls. Results The results show that erythrocyte superoxide dismutase activity and plasma nitrite/nitrate levels are high in vitiligo patients. Conclusions Our study confirms that oxidative stress is involved in the pathophysiology of vitiligo, as indicated by the high levels of erythrocyte superoxide dismutase activity and plasma nitrite/nitrate.Öğe The effect of sustained and local administration of epidermal growth factor on improving bilateral testicular tissue after torsion(Springer, 2004) Uguralp, S; Karabulut, AB; Mizrak, B; Kaymaz, F; Kiziltay, A; Hasirci, NEpidermal growth factor (EGF) modulates Leydig cell proliferation, steroidogenesis, spermiogenesis, and Sertoli cell activity. It plays an important role in repairing ischemia-reperfusion injury in different tissues. The aim of this study was to evaluate the effects of sustained and local administration of EGF on improving bilateral testicular tissue after torsion. A total of 57 Wistar albino rats were used. For the EGF transport system, 1x2 cm gelatin films containing 2 mug EGF were used. Torsion was created by rotating the right testis 720degrees in a clockwise direction for 4 h in all groups except the control group. Then, in the torsion group, bilateral orchiectomy was performed. After returning the torsioned ipsilateral testes to their normal state, the bilateral testes were wrapped by 1x2 cm unloaded gelatin films in the gelatin (G7 and G21) groups and, by 2 mug EGF loaded gelatin films in the EGF 7 and EGF 21 groups. The testes were removed on the seventh and 21st days, respectively, for biochemical and histological examination. Histologically, Johnsen's spermatogenesis criteria and mean seminiferous tubule diameter (MSTD) measurements were used. The EGF7 group did not show significant loss of Sertoli cells, while in the G7 group the number of these cells decreased. The ipsilateral ischemic testis of the EGF21 group showed Leydig cell hyperplasia, and the contralateral non-ischemic testes in this group were similar to the control group. In the G21 group, the bilateral testes showed Sertoli cell only syndrome in some sections, and most of the cells were undergoing apoptosis. The mean spermatogenesis scores and MSTD in the EGF7 and EGF21 groups were higher than in the G7 and G21 groups (P<0.05). Malondialdehyde levels were significantly lower in the EGF groups than in the G groups (P<0.05). Glutathione peroxidase (GSH-Px) levels in the G21 group were significantly higher than in the EGF21 group. Our study shows that local and sustained EGF release after testicular torsion improves bilateral testicular injury. EGF administration may be a new treatment choice for bilaterally injured testis after detorsion without removing the twisted testis.Öğe Effect of the treatment of brucellosis on leukocyte superoxide dismutase activity and plasma nitric oxide level(Sage Publications Inc, 2005) Karabulut, AB; Sonmez, E; Bayindir, YBackground: The mechanisms by which brucellae evade intracellular killing by polymorphonuclear leukocytes are incompletely understood. In this study, we evaluated changes of leukocyte superoxide dismutase (SOD) activity and plasma total nitrite as an indicator of nitric oxide (NO) levels during brucellosis therapy. Methods: Thirty-two patients with acute brucellosis, 27 patients with chronic brucellosis and 30 healthy controls were included in the study. Patients with acute brucellosis were tested for leukocyte SOD activity and plasma total nitrite levels before, during (21st day), and at the end (45th day) of the combined therapy of rifampicin and doxycycline. The same parameters were also investigated in chronic cases and controls. Results: The SOD activities were lower in patients with acute brucellosis before therapy compared with those 21 and 45 days after starting therapy (P < 0.001). In contrast, total nitrite levels did not change significantly (P > 0.05). Conclusions: In the present study, leukocyte SOD activity was found to be decreased in patients with acute brucellosis. Enzyme activity was increased by treatment, finally reaching the activity of healthy controls. Using an antioxidant agent in addition to classical antimicrobial therapy for acute brucellosis might be a therapeutic approach.Öğe Effects of pentoxifylline and vitamin E on the bilateral ovary after experimental ovarian ischemia(Georg Thieme Verlag Kg, 2005) Uguralp, S; Karabulut, AB; Mizrak, BPentoxifylline (PTX) and vitamin E inhibit the release of superoxide and hydroxyl radicals, and PTX improves capillary flow and tissue oxygenation. This experimental study was designed to determine the effects of PTX and vitamin E in the ovary after unilateral ovarian ischemia reperfusion (I-R) in albino Wistar rats. A vascular clamp was placed on the left ovary for 4 hours in all groups except for the control group. Following this, in the ischemia (1) group bilateral ovariectomy was performed. Saline, PTX, vitamin E, and PTX plus vitamin E were infused 30 min before reperfusion in the reperfusion (R), pentoxifylline (P), vitamin E (E), and pentoxifylline plus vitamin E (PE) groups, respectively. After 4 hours of reperfusion, the ovaries were removed for biochemical and histologic examination. MDA levels of bilateral ovaries in the PE group were significantly lower than in the E group (p < 0.0033). NO levels of bilateral ovaries in the PE group were significantly lower than in the P and E groups (p < 0.0033). Massive hemorrhage was determined in the ipsilateral ovaries of the R group. Hemorrhage was minimal or moderate in the ipsilateral ovaries of other groups. The contralateral ovaries showed congestion in different degrees. The contralateral ovaries of the group PE and the bilateral ovaries of the control group showed no pathological changes. PTX and vitamin E given together seems to be more effective in reducing I-R injury in ovarian tissue compared to administration of PTX, or vitamin E alone. However, further studies are required to evaluate the effective dose and duration of PTX and vitamin E on bilateral ovaries.Öğe Hydrophobic nature of rat lymph chylomicrons(Elsevier Science Bv, 2004) Güldür, T; Karabulut, AB; Bayraktar, N; Kaynar, ÖBackground: A typical molecular structure of a lipoprotein is composed of hydrophobic lipids at the core and hydrophilic apolipoprotein side chains and lipid head groups at the surface. Some of the hydrophobic characteristics of rat lymph chylomicrons were investigated. Methods: Thoracic duct was cannulated and lymph was collected overnight. Chylomicrons (>100 rim) were isolated by ultracentrifugation at 4 x 10(6) x g min. Since particle aggregation is a characteristic of hydrophobic nature of lipoproteins, as an index of aggregation, the turbidity generated by vortexing and storage of chylomicrons was measured spectrophotometrically at 680 nm. We also assessed the ability of chylomicrons to interact with five different hydrophobic interaction chromatography (HIC) media. Results: Neither shaking nor prolonged storage at 4 degreesC produced an increase in the optical density of chylomicron solution indicating no aggregation took place. Typical elution profiles of chylomicrons through octyl, phenyl (high substance) and butyl sepharose columns showed two peaks. Peak I material emerged with 4 mol/l NaCl in a position corresponding to the void volume and peak II material eluted with water. Phenyl sepharose (high performance) media exhibited the maximum binding strength towards chylomicrons among the five different media. In the case of pheryl sepharose (low substance) column, an additional material was eluted with 3 mol/l NaCl between peaks I and II. These results indicate the heterogeneity of chylomicron surface hydrophobicity. Conclusion: Since particle aggregation is a characteristics of hydrophobicity of lipoproteins and believed to be an underlying cause of atherosclerosis, fractionation of lipoproteins by hydrophobic interaction chromatography may introduce a new approach into the assessment of lipoprotein atherogeneicity. (C) 2004 Elsevier B.V. All rights reserved.Öğe Interferon-alpha reduces the development of experimental necrotizing enterocolitis(Academic Press Ltd- Elsevier Science Ltd, 2004) Uguralp, S; Mizrak, B; Karabulut, AB; Gürbüz, N; Demircan, MCytokines had important role in the pathogenesis of necrotizing enterocolitis (NEC). The aim of this study is to investigate if IFN-alpha has a prophylaxic, effect on experimental NEC development in newborn rat pups. Twenty eight Wistar Albino newborn rat pups were divided into three groups. Control group rats were breast-fed, NEC group and interferon (IFN) group rat pups were hand-fed with premature newborn formula. IFN-alpha was administered subcutaneously at a dose of 50,000 IU/rat/day in IFN group. NEC was induced experimentally by cold stress twice a day in IFN and NEC groups. On the fourth day, the rats were killed, and all the intestine were removed to determine the tissue level of malonaldehyde (MDA) and histologic changes. The microscopic lesions in the NEC group rats were virtually the same as those seen in neonatal NEC, with severe separation of submucosa and/or lamina propria, loss of villi and in some cases necrosis to extention the muscularis. In contrast, in the rats treated with IFN, lesions were moderate separation of submucosa and/or lamina propria, edema in submucosal and muscular layers. Intestinal injury score and MDA levels in NEC group were significantly higher than in the IFN group (P < 0.05). In conclusion it was suggested that IFN-a was effective in reducing the severity of NEC in rat pups. (C) 2004 Elsevier Ltd. All rights reserved.Öğe Maternal and fetal plasma adenosine deaminase, xanthine oxidase and malondialdehyde levels in pre-eclampsia(Wiley, 2005) Karabulut, AB; Kafkasli, A; Burak, F; Gozukara, EMThe aim of this study was to evaluate maternal-fetal plasma adenosine deaminase, xanthine oxidase (ADA, XO) activity and malondialdehyde (MDA) levels and the relationship between them in pre-eclampsia. Maternal and umbilical cord whole blood samples were taken from 29 pre-eclamptic and 33 normal pregnants. The plasma ADA, XO activities as well as MDA levels were assayed by spectrophotometric methods. MDA levels and ADA, XO activities were found to be higher in maternal and fetal plasma in pre-eclamptics than in normal pregnancy. The differences were statistically significant between groups (p < 0.05). Increased maternal-fetal plasma XO and ADA activities, its a marker of immunological disorder, may be related to the pathogenesis of pre-eclampsia. In addition, increased MDA levels may be a reflection of increased oxidative stress in pre-eclamptics and their fetuses. Copyright (c) 2004 John Wiley & Sons, Ltd.Öğe Protective effect of melatonin against oxidative stress on adhesion formation in the rat cecum and uterine horn model(Pergamon-Elsevier Science Ltd, 2005) Ara, C; Kirimlioglu, H; Karabulut, AB; Coban, S; Hascalik, S; Celik, O; Yilmaz, SThis experimental study was designed to evaluate the degree of adhesion formation and peritoneal tissue levels of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) and the effect of melatonin on these metabolites in a postoperative intraperitoneal adhesion formation model in rats. Thirty adult female Wistar albino rats were subjected to standardized lesions by cecal and uterine horn abrasion and were randomly divided into three groups. Control rats were treated with 5% ethanol. Melatonin treated rats received 4 mg/kg melatonin before closure and for 10 consecutive days intraperitoneally after surgery. Rats in the sham operation group underwent a surgical procedure similar to the other groups however the peritoneal abrasion was not performed. On postoperative day 10 relaparatomy was performed. After the assessment of the adhesions, the rats in each group were sacrificed and peritoneal tissues were harvested to determine the tissue levels of MDA, GSH and NO activity. Adhesion formation scores in the melatonin group were significantly lower than that of control and sham group (p < 0.01 and p < 0.02, respectively). Tissue levels of MDA and NO were significantly lower in the melatonin treated rats when compared with control and sham groups. The levels of GSH in the melatonin treated rats were significantly higher than those of control and sham groups (p < 0.01). The results demonstrate that in this experimental model, intraperitoneal administration of melatonin decreases the extent of peritoneal adhesions and causes a decrease in MDA and NO and an increase in GSH levels. (c) 2005 Elsevier Inc. All rights reserved.Öğe Protective effect of resveratrol against oxidative stress in cholestasis(Academic Press Inc Elsevier Science, 2005) Ara, C; Kirimlioglu, H; Karabulut, AB; Coban, S; Ay, S; Harputluoglu, M; Kirimlioglu, VBackground. We investigated the protective role of resveratrol in rat liver injuries induced by chronic biliary obstruction. Materials and methods. Secondary biliary cirrhosis was induced by bile duct ligation for 28 days. Swiss albino rats were divided into the three following groups: group 1: sham (n = 7); group 2: bile duct ligation (n = 7); group 3: bile duct ligation plus resveratrol (n = 7). Bile duct ligation plus resveratrol group received 10 mg(kg dose of resveratrol intraperitoneally daily for 28 days. Liver damage and cholestasis were determined by the biochemical and the pathologic examination. Results. The present data showed a decrease in both plasma bilirubin levels and aspartate aminotransferase and alanine aminotransferase levels in the resveratrol-treated rats, when compared with bile duct ligation group (P < 0.05). In the resveratrol-treated rats, tissue levels of malondialdehyde and nitric oxide were significantly lower than that of the bile duct ligation (P < 0.002). The levels of glutathione in resveratrol-treated rats were significantly higher than that in bile duct ligation group (P < 0.004). The levels of interleukin-1 alpha, interleukin-6, and tumor necrosis factor-alpha in resveratrol group were significantly lower than that in bile duct ligation group (P < 0.004, P < 0.001, P < 0.001, respectively). Administration of resveratrol in the rats with biliary obstruction resulted in inhibition of ductular proliferation and lymphocytic inflammation. Conclusion. The present study demonstrates that intraperitoneal administration of resveratrol in bile duct ligated rats maintained antioxidant defenses and reduces liver oxidative damage and ductular proliferation. This effect of resveratrol may be useful in the preservation of liver function in cholestasis. (c) 2005 Elsevier Inc. All rights reserved.Öğe Protective effect of resveratrol against renal oxidative stress in cholestasis(Taylor & Francis Inc, 2005) Ara, C; Karabulut, AB; Kirimlioglu, H; Coban, S; Ugras, M; Kirimliglu, V; Yilmaz, SBackground/aims. This experimental study was designed to evaluate histological changes of the kidney and renal tissue levels of malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) and the effect of resveratrol on these metabolites after bile duct ligation in rats. Methods. Secondary biliary cirrhosis was induced by bile duct ligation for 28 days. Swiss albino rats were divided into three groups. Group 1: Sham (n=7), Group 2: Bile duct ligation (n=7), Group 3: Bile duct ligation plus resveratrol (n=7). Bile duct ligation (BDL) plus resveratrol group received 10 mgr/kg dose of resveratrol intraperitoneally daily throughout 28 days. Kidney tissues were harvested to determine the tissue levels of MDA, GSH, and NO activity. Liver and kidney tissues were removed for light microscopic evaluation. Results. Cholestasis was determined by biochemical and pathologic examination. In the resveratrol-treated rats, levels of MDA were significantly lower than those of the BDL group (p<0.04). The levels of GSH in the resveratrol-treated rats were significantly higher than those in the BDL group (p<0.01). The levels of NO in the resveratrol group were significantly lower than those in the BDL group (p<0.01). Conclusion. The present study demonstrates that intraperitoneal administration of resveratrol in bile duct ligated rats maintains antioxidant defenses and reduces kidney oxidative damage. This effect of resveratrol may be useful in the preservation of renal oxidative stress in cholestasis.Öğe Protective effects of resveratrol on spleen and ileum in rats subjected to ischemia-reperfusion(Elsevier Science Inc, 2006) Karabulut, AB; Kirimlioglu, V; Kirimlioglu, H; Yilmaz, S; Isik, B; Isikgil, OResveratrol is as an antioxidant with free radical-scavenging activity and finds its clinical application in the prevention of postischernic tissue injury following solid organ transplantation. This study investigates the effect of Resveratrol on spleen and ileum tissues subjected to hepatic ischemia-reperfusion (I/R) in rats. Twenty-four rats were recruited in the study as follows: group A: I/R (n = 8), group B: I/R + Resveratrol (it = 8), and group C: sham operation (n = 8). After intraperitonealy pretreatment of eight rats with resveratrol (15 mg/kg/d) for 5 days, 16 rats were subjected to 45 minutes of hepatic ischemia followed by 30 minutes reperfusion period. Resveratrol was given 15 minutes prior to ischemia and just before the reperfusion in rats. After reperfusion period all rats were sacrified. Spleen and ileum tissues were examined spectrophotometrically to measure malondialdehyde (MDA), glutathione (GSH), and total nitrite, nitrate as an end product of nitric oxide (NO) levels. Concerning the spleen, statistically significant decrease of GSH and increase of MDA and NO levels were found group A when compared to groups B and C (P = .040, P = .004, and P = .001 group A vs group B; P = .05, P = .003, and P = .001 group A vs group C, respectively). Parallel results were obtained in ileum. A statistically significant decrease in GSH and an increase in MDA and NO levels in group A in respect to group B and group C was obtained (P = .048, P = .034, and P = .00.1 group A vs group B; P = .004, P = .001, and P = .003 group A vs group C, respectively). The result of this study shows that resveratrol has a protective effect on spleen and ileal mitochondrial oxidative stress in rats subjected to I/R.Öğe Resveratrol reduces ischemia reperfusion injury after experimental testicular torsion(Georg Thieme Verlag Kg, 2005) Uguralp, S; Mizrak, B; Karabulut, ABThe aim of the study was to evaluate the effects of resveratrol on testicular ischemia reperfusion injury. Forty Wistar albino rats were divided into 4 groups. Torsions (ischemia) were created by rotating the right testis 720° in a clockwise direction for 4 hours in all groups except the control group. In the torsion group after 4 hours' ischemia bilateral orchiectomy was performed. In the detorsion group, saline was injected by an intraperitoneal route, 30 min before detorsion (reperfusion). In the resveratrol group, 30 mg/kg resveratrol was injected by an intraperitoneal route, 30 min before detorsion. In the detorsion and resveratrol groups, the bilateral testes were removed after 20 hours of detorsion. In all groups, the tissue levels of malondialdehyde (MDA) and glutathione (GSH) and histological changes were determined. In rats treated with resveratrol, MDA levels (138 ± 25 nmol/mg protein) were significantly decreased compared with torsion (426 ± 178 nmol/mg protein) and detorsion (370 ± 76 nmol/mg protein) groups (p < 0.05). GSH levels (6.54 ± 0.8 ? mol/g wet tissue) were significantly increased compared with torsion (4.61 ± 0.4 ? mol/g wet tissue) and detorsion groups (5.24 ± 0.9 ? mol/g wet tissue) (p < 0.05). The mean testicular tissue injury score in the resveratrol group was significantly lower than in torsion and detorsion groups (p < 0.05). The present study demonstrates that intraperitoneal administration of resveratrol in rats may protect testis against injury associated with reperfusion.Öğe Tumour necrosis factor ?, lipid peroxidation and NO• are increased and associated with decreased free-radical scavenging enzymes in patients with Weill-Marchesani syndrome(Hindawi Ltd, 2004) Evereklioglu, C; Turkoz, Y; Calis, M; Duygulu, F; Karabulut, ABAIM: Weill-Marchesani syndrome (WMS) is a rare systemic disorder with both autosomal recessive and dominant inheritances. Accumulation of reactive oxygen species such as O-2(.-), H2O2 and OH. causes lipid peroxidation (LPO), whereas antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSHPx)) mediate defence against oxidative stress. Excess tumour necrosis factor (TNF)-alpha and NO. react with O-2(.-) and cause further antioxidant depletion with an increase in mutation frequency by H2O2. This study investigated the levels of SOD, GSHPx, catalase (CAT), TNF-alpha, NO. and LPO in patients with WMS. Methods: A group of 10 WMS patients (four males, six females; age, 26.5 +/- 19.0 years) and 10 age-matched and sex-matched controls (five males, five females; age, 27.3 +/- 18.2 years) were included. Serum TNF-alpha levels were determined by a spectrophotometer technique using immulite chemiluminescent immunometric assay. Malondialdehyde (MDA) was determined in plasma; CAT in red blood cells (RBCs), and SOD and GSHPx in both plasma and RBCs. Total serum NO. levels were evaluated by Griess reaction. Results: Mean levels of TNF-alpha (8.3 +/- 0.6 pg/ml) in WMS patients were significantly (p < 0.001) higher than controls (4.3 +/- 0.2 pg/ml). Plasma MDA levels in patients and controls were 5.4 +/- 0.8 and 1.8 +/- 0.6 mu mol/l, respectively, and the difference was significant (p = 0.0002). SOD and GSHPx activities were significantly lower in both RBCs and plasma of WMS than in controls (RBC-SOD, 3981.9 +/- 626.6 versus 5261.6 +/- 523.0 U/g haemoglobin (Hb), p = 0.0005; plasma-SOD, 529.4 +/- 49.3 versus 713.4 +/- 55.7 U/g protein, p = 0.0002; RBC-GSHPx, 682.7 +/- 42.0 versus 756.5 +/- 47.6 U/g Hb, p = 0.0011; plasma-GSHPx, 107.3 +/- 15.0 versus 131.4 +/- 19.7 U/g protein, p = 0.0113). In addition, serum NO center dot (NO2- + NO3-) levels were also significantly (p = 0.0002) increased in WMS patients (54.4 +/- 5.7 versus 26.9 +/- 6.7 mumol/l). RBC-CAT levels were similar between groups (125.6 +/- 21.3 versus 131.0 +/- 21.5 k/g Hb, p = 0.8798). Conclusions: The elevated LPO, TNF-alpha and NO. with decreased antioxidant enzyme activities indicated impaired antioxidative defence mechanisms with an oxidative injury and cell toxicity in WMS patients. The use of multiple antioxidants and free radical scavengers might be helpful in this genetic disorder.
