Seval Aydin

Maternal plasma levels of cytokines in normal and preeclamptic pregnancies and their relationship with diastolic blood pressure and fibronectin levels.

Background.  To determine the plasma concentrations of placental growth factor (PLGF), vascular endothelial growth factor (VEGF), transforming growth factor‐β1 (TGF‐β1), soluble tumor necrosis factor α receptor (sTNFp55), interleukin‐2 receptor (IL‐2R), and interleukins 6 and 10 (IL‐6, IL‐10) in normotensive and preeclamptic women, and to evaluate the correlations between these cytokines and the diastolic blood pressure and fibronectin levels.

Changes in Leptin, Plasminogen Activator Factor and Oxidative Stress in Morbidly Obese Patients following Open and Laparoscopic Swedish Adjustable Gastric Banding

Background: Oxidative stress is increased in obesity, leading to endothelial dysfunction, atherogenesis, and platelet aggregation. The purpose of this study was to determine the effects of weight loss after bariatric surgery on serum lipids, malondialdehyde (MDA, a marker of oxidative stress), oxidized low-density lipoprotein (oxLDL, which is increased in obesity and causes endothelial dysfunction), paraoxonase (PON-1, which inhibits lipid peroxidation), leptin and plasminogen activator inhibitor type-1 (PAI-1, which contributes to a thrombotic state). Methods: 40 morbidly obese patients had insertion of a Swedish adjustable gastric band (SAGB). A lipid profile, MDA, oxLDL, PON-1, leptin and PAI-1 levels were drawn before and 6 months after the operation. 20 patients underwent open (Group 1) and 20 laparoscopic (Group 2) SAGB, to compare the systemic inflammatory response of the two approaches. Results: Patient demographics, indications for surgery, and postoperative results were no different between the groups. Postoperative BMI and concentrations of lipid, MDA, oxLDL, leptin and PAI-1 decreased significantly in both groups. PON-1 activity increased and was negatively correlated with BMI (r=-0.618, P< 0.01), MDA (r=-0.735, P<0.001), oxLDL (r=-0.701, P< 0.01), leptin (r=-0.626, P<0.01) and PAI-1 (r=-0.461, P<0.05). There was a correlation between BMI and MDA (r=0.790, P <0.001), and also leptin (r=0.900, P<0.001) and PAI-1 (r=0.888, P=0.001). There was no correlation between BMI and oxLDL. Conclusion: These findings support the hypothesis that in morbid obesity, weight loss after surgery has positive effects on fibrinolytic function, oxidative stress and antioxidant activity. Both operative approaches had similar effects in this study.

Plasma malondialdehyde, superoxide dismutase, sE-selectin, fibronectin, endothelin-1 and nitric oxide levels in women with preeclampsia

OBJECTIVE The purpose of this study was to determine plasma malondialdehyde (MDA), superoxide dismutase (SOD), soluble E-selectin (sE-selectin), fibronectin, endothelin-1 (ET-1) and nitric oxide (NO) levels in women with preeclampsia and to find out the relations of diastolic blood pressure with these variables. STUDY DESIGN We performed a case-control study consisting of randomly selected 34 healthy pregnant women and 35 patients diagnosed as preeclampsia. Lipoperoxidation was ascertained by the formation of MDA. SOD activity was determined by the method of Sun et al. Plasma concentration of NO was estimated using colorimetric assay. Plasma ET-1 and sE-selectin were measured by enzyme-linked immunosorbent assay (ELISA). A nephelometric method for fibronectin quantitation was used. RESULTS The mean plasma level of MDA was significantly higher and SOD was significantly lower in preeclamptic pregnancies (P<0.001). Plasma concentrations of fibronectin, sE-selectin and ET-1 were significantly increased, whereas NO was significantly decreased in women with preeclampsia than normotensive women (P<0.001). CONCLUSION Increased plasma levels of MDA, fibronectin, sE-selectin, ET-1, and decreased plasma levels of NO and SOD in preeclamptic patients suggest that poorly perfused fetoplacental unit is the origin of oxygen free radicals and lipid peroxides.

The plasma and placental levels of malondialdehyde, glutathione and superoxide dismutase in pre-eclampsia.

The aim of the study is to investigate the plasma and placental levels of malondialdehyde, glutathione and superoxide dismutase in normotensive and pre-eclamptic pregnancies. Peripheral venous blood samples were collected before labour (35·3 - 1·1 and 34·2 - 3·4 weeks for normotensive and pre-eclamptic, respectively) and placental tissues was obtained after delivery from 34 pre-eclampsia and 33 normotensive pregnancies. The mean plasma and placental levels of malondialdehyde were significantly higher, glutathione and superoxide dismutase levels were significantly lower in pre-eclamptic compared with normotensive patients ( P < 0·01). The plasma and placental levels of malondialdehyde significantly increased, glutathione and superoxide dismutase significantly decreased with the increments in diastolic blood pressure. As a conclusion maternal circulating and placental tissue levels of lipid peroxides increase whereas antioxidants decrease in pre-eclampsia. The magnitude of oxidative stress and antioxidant changes correlate well with diastolic blood pressure.

Melatonin reduces dimethylnitrosamine-induced liver fibrosis in rats

Abstract:  Increased deposition of the extracellular matrix components, particularly collagen, is a central phenomenon in liver fibrosis. Stellate cells, the central mediators in the pathogenesis of fibrosis are activated by free radicals, and synthesize collagen. Melatonin is a potent physiological scavenger of hydroxyl radicals. Melatonin has also been shown to be involved in the inhibitory regulation of collagen content in tissues. At present, no effective treatment of liver fibrosis is available for clinical use. We aimed to test the effects of melatonin on dimethylnitrosamine (DMN)‐induced liver damage in rats. Wistar albino rats were injected with DMN intraperitoneally. Following a single dose of 40 mg/kg DMN, either saline (DMN) or 100 mg/kg daily melatonin was administered for 14 days. In other rats, physiologic saline or melatonin were injected for 14 days, following a single injection of saline as control. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) levels were evaluated in blood and tissue homogenates. DMN caused hepatic fibrotic changes, whereas melatonin suppressed these changes in five of 14 rats (P < 0.05). DMN administration resulted in increased hydroxyproline and MDA levels, and decreased GSH and SOD levels, whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin functions as a potent fibrosuppressant and antioxidant, and may be a therapeutic choice.

Vitamin E has a dual effect of anti-inflammatory and antioxidant activities in acetic acid-induced ulcerative colitis in rats.

BACKGROUND Increased free radical production, decreased antioxidant capacity and excessive inflammation are well-known features in the pathogenesis of inflammatory bowel disease. Vitamin E is a powerful antioxidant and a scavenger of hydroxyl radicals, and it has been shown to have anti-inflammatory activities in tissues. We investigated the effects of vitamin E on inflammatory activities using an acetic acid (AA)-induced ulcerative colitis model in rats. METHODS Wistar rats were divided into 4 groups. Acetic acid was given to 2 groups of animals to induce colitis while the other 2 groups received saline intrarectally. One AA-induced colitis group and 1 control group received vitamin E (30 U/kg/d) intraperitoneally and the pair groups received saline. After 4 days, we evaluated colonic changes biochemically by measuring proinflammatory cytokine levels in tissue homogenates and by histopathologic examination. RESULTS Acetic acid caused colonic mucosal injury, whereas vitamin E administration suppressed these changes in the AA-induced colitis group (p < 0.001). Administration of AA resulted in increased levels of tumour necrosis factor-α, interleukin-1β, interleukin-6, myeloperoxidase and malondialdehyde, and decreased levels of glutathione and superoxide dismutase; vitamin E reversed these effects (all p < 0.001). CONCLUSION Our study proposes that vitamin E is an effective anti-inflammatory and antioxidant and may be a promising therapeutic option for ulcerative colitis.

Oxidative stress in white coat hypertension; role of paraoxonase.

Oxidative stress in sustained hypertension was shown with several biochemical parameters. Oxidized low-density lipoprotein (oxLDL) plays an important role during the atherosclerosis process and paraoxonase (PON1) can significantly inhibit lipid peroxidation. Serum PON1 activity, oxLDL and malondialdehyde (MDA) concentrations and their relationship with serum lipid parameters and systolic and diastolic blood pressures (SBP and DBP) were determined in subjects with white coat hypertension (WCH), sustained hypertension (HT) and normotension (NT). The study group consisted of a total of 86 subjects, 30 with WCH (14 male, 16 female subjects), 30 with HT (13 male, 17 female subjects) and 26 with NT (12 male, 14 female subjects). Both white coat hypertensive and hypertensive subjects had significantly higher levels of MDA than normotensives (P<0.026 and P<0.001, respectively). The oxLDL level of the HT group was significantly higher than the NT group (P<0.023). The WCH group had an oxLDL level similar to both hypertensive and normotensive groups. HT and WCH groups had significantly lower PON1 levels than the normotensive group (P<0.001). oxLDL correlated with MDA positively (P=0.008), and PON1 negatively (P=0.008). A negative correlation between MDA and PON1 (P=0.014) was detected. MDA correlated positively with both SBP and DBP (P=0.001), while PON1 correlated with both of them negatively (P=0.01 and P=0.008, respectively). OxLDL correlated with diastolic blood pressure positively (P=0.008). Our data demonstrate that oxidative stress increase in WCH is associated with a decrease in PON1 activity. The reduction in PON1 activity may be one of the factors leading to an increase in oxidative status in WCH.

Circulating Oxidized Low-Density Lipoprotein and Paraoxonase Activity in Preeclampsia

Preeclampsia is one of the most frequent complications of pregnancy, however, little is known about its etiology. The objective of this study was to investigate the association of oxidized low-density lipoprotein (oxLDL) and paraoxonase (PON1) activity in women with either preeclampsia or normotensive (NT) pregnancy. The study groups included 41 pregnant women with preeclampsia and 33 normotensive pregnant women. In all patients maternal serum total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TGs) were measured using enzymatic methods. Serum PON1 activities and malondialdehyde (MDA) concentrations were measured by spectrophotometric methods, and oxLDL was measured by enzyme-linked immunoassay (ELISA). Serum concentrations of lipid parameters (TC, LDL, VLDL, and TGs) were significantly higher in preeclampsia compared with NT controls (p < 0.001, p < 0.05, p < 0.05, and p < 0.001, respectively). Serum concentrations of MDA and oxLDL were significantly higher, while PON1 activity was significantly lower in preeclampsia compared with NT controls (p < 0.001, p < 0.001, and p < 0.001, respectively). A positive correlation was detected between oxLDL and MDA (r = 0.876), and a negative correlation was detected between both MDA and oxLDL and PON1 (r = –0.837 and r = –0.759, respectively). Our data demonstrate that preeclampsia is associated with increased oxLDL and decreased PON1 activity. Elevated oxidative stress, oxLDL, dyslipidemia and decreased PON1 activities may cause vascular endothelial damage and contribute to the pathophysiology of preeclampsia.

Copper-mediated oxidative stress in rat liver

Copper is an essential trace element with various biological functions. Excess copper, however, is extremely toxic, leading to many pathological conditions that are consistent with oxidative damage to membranes and molecules. Exposure to high levels of copper results in various changes in the tissues. In liver, hypertrophy of hepatocytes, hepatitis, hepatocellular necrosis, and hepatocellular death are the results. Lipid peroxidation causes dysfunction in the cell membrane, decreased fluidity, inactivation of receptors and enzymes, and changes ion permeability. In this study, we aimed to determine the effect of copper on oxidative and antioxidative substances in plasma and liver tissue in a rat model.Sixteen male Sprague—Dawley rats were divided into two groups: Group 1 rats included control rats given tap water. Group 2 rats were given water containing copper in a dose of 100 µg/mL. All rats were sacrificed at 4 wk under ether anesthesia. Plasma and liver superoxide dismutase (SOD) activities, plasma and liver MDA (malondialdehyde) levels, and liver glutathione (GSH) levels were studied. Plasma and liver SOD activities were found to be higher in group 2 than those in group 1. Although plasma MDA levels were higher in group 2, MDA levels in liver tissues were comparable. Liver tissue glutathione levels were lower in group 2. It was concluded that although copper is needed in trace amounts, an excess amount is toxic for the organism. It increases lipid peroxidation and depletes GSH reserves, which makes the organism more vulnerable to other oxidative challenges.

Hyperhomocysteinemia in inflammatory bowel disease patients without past intestinal resections: correlations with cobalamin, pyridoxine, folate concentrations, acute phase reactants, disease activity, and prior thromboembolic complications.

Objective Homocysteine is a sulfur-containing amino acid formed during the demethylation of methionine and high levels of this amino acid is a known risk factor for both arterial and also venous thromboembolic complications. Deficiencies of cobalamin, folate, and pyridoxine may predispose subjects to hyperhomocysteinemia, a common phenomenon in inflammatory bowel disease (IBD) patients. The aim of this study was to identify the prevalence, risk factors of hyperhomocysteinemia and its correlation with prior thromboembolic events in an IBD cohort without past intestinal resections. Methods In this prospective study, we studied the concentrations of homocysteine, cobalamin, folate, and pyridoxine in 105 consecutive patients with IBD, of whom 11 had a prior history of thromboembolic complications. Data regarding smoking habits, medication use, disease location, and severity were gathered and patients with past intestinal resections were excluded. Age-matched and sex-matched 85 healthy volunteers served as controls and multivariate regression analysis was performed to find out independent predictors of hyperhomocysteinemia. Results The mean age (±SD) in the IBD cohort was 38.69±12.13 years, and 51% were male. The mean age in the control group was 37.61±10.05 years, and 52% were male. Homocysteine concentrations in patients were higher [16.35 μmol/L (range 6.82 to 48.15) vs. 9.60 μmol/L (range 4.97 to 17.39), P=0.000] and hyperhomocysteinemia had a higher prevalence in patients than in the controls (56.2% vs. 4.7%, χ2=56.179, P=0.000), thus IBD significantly increased the risk of hyperhomocysteinemia [odds ratio=25.973 (95% confidence interval: 8.861-76.128)]. Homocysteine concentrations in patients with a history of thrombosis were not higher than those without a history of thrombosis [16.29 μmol/L (range 8.45 to 34.75) vs. 16.36 μmol/L (range 6.82 to 48.15), not significant]. Hyperhomocysteinemia was found in 54.5% of patients with thrombosis and 56.4% of patients without thrombosis (not significant). On stepwise regression analysis, plasma cobalamin level, albumin concentration, erythrocyte sedimentation rate, and platelet count were found to be independent predictors of elevated homocysteine levels. Conclusions IBD patients have a higher prevalence of hyperhomocysteinemia than do healthy controls and elevated homocysteine levels are independently associated with lower serum cobalamin, albumin levels and elevated erythrocyte sedimentation rate, and platelet count. There is no correlation between hyperhomocysteinemia and a history of prior thromboembolic events.