Zehra Serdar

Lipid and protein oxidation and antioxidant function in women with mild and severe preeclampsia.

Abstract Object. The aim of this study was to evaluate the lipid and protein oxidation and antioxidant function in preeclampsia patients and in normotensive pregnant women, as well as, to assess an association with the severity of the disease. Method. The study was carried out in 30 patients with mild preeclampsia, 30 with severe preeclampsia, and in 50 normotensive pregnant women during the third trimester of pregnancy. Lipid peroxides in serum, placental and decidual tissues and serum protein carbonyls and some of the antioxidants were measured by spectrophotometric methods. One-way analysis of variance, chi-square test and Pearson correlation test were used for the statistical analyses. Logistic regression procedures were used to calculate odds ratios (OR). Results. Lipid peroxides in serum, placenta and decidua basalis and protein carbonyls in serum were significantly increased, and vitamin E and total carotene levels in serum were significantly decreased especially in women with severe preeclampsia compared with mild preeclampsia and controls. A significant correlation was detected between diastolic blood pressure and lipid peroxides in serum, placental and decidual tissues and serum protein carbonyls. Furthermore, there was significant correlation between antioxidant vitamins and lipid and protein oxidation products in severe preeclamptic patients. Also, logistic regression analysis showed that changes in serum, placental and decidual lipid peroxides and serum protein carbonyls, vitamin E and total carotene concentrations were significantly associated with preeclampsia. Conclusion. Our findings suggest that lipid and protein oxidation may be an important factor in the pathogenesis of preeclampsia. Since antioxidant vitamins are significantly decreased in both severe and mild preeclamptic pregnants, early supplementation with antioxidants may be beneficial in preeclamptic patients.

Placental and decidual lipid peroxidation and antioxidant defenses in preeclampsia: Lipid peroxidation in preeclampsia

We evaluated lipid peroxidation in serum, placenta and decidua basalis and antioxidant defenses in preeclampsia and normal pregnancy. The study group consisted of 70 women with preeclampsia and 72 healthy pregnant women. Lipid peroxides in serum, placenta and decidua basalis, and serum vitamin E and total carotene were measured by spectrophotometric methods. Unpaired Students t-test, chi(2)-test and Pearson correlation test were used for the statistical analyses. Levels of lipid peroxides in serum, placenta and decidua basalis were markedly higher; and serum vitamin E, total carotene, bilirubin, albumin levels were markedly lower in preeclamptic pregnants compared with healthy pregnant women. Our findings demonstrated that both placenta and decidua basalis tissues may be a source of lipid peroxides in preeclamptic pregnancies. Prophylactic antioxidant therapy may abate the disease process. Further studies are needed to clarify the pathophysiology of preeclampsia and effectiveness of prophylactic antioxidant therapy in preeclampsia.

Effect of N-acetylcysteine on oxidative stress and ventricular function in patients with myocardial infarction.

Recent evidence suggests that postischemic myocardial dysfunction (“stunning”) may be mediated by oxygen free radicals. Various studies have reported the beneficial effects of antioxidants in ischemia–reperfusion injury. The aim of this study was to assess the effect of N-acetylcysteine (NAC) treatment on oxidative stress, infarct size, and left ventricular (LV) function, as adjunct therapy in myocardial infarction (MI). Patients with acute MI received either 15 g NAC infused over 24 h (n = 15) or no NAC (n = 15), combined with streptokinase. Peripheral venous blood was serially sampled to measure creatine kinase (CK)-MB levels. Plasma malondialdehyde (MDA) level was measured at admission and after 4 and 24 h. Echocardiography was performed within 3 days of MI and after 3 months. At admission, plasma MDA levels were not different between the groups. In the NAC-treated patients plasma MDA levels decreased, whereas in the nontreated NAC patients MDA levels increased at 4 and 24 h (P < 0.01 and P < 0.001, respectively). Left ventricular ejection fraction was higher (P < 0.05) and LV end-systolic and end-diastolic diameters were lower (P < 0.001 and P < 0.001) in patients receiving NAC on day 3. Left ventricular wall motion score index was significantly lower in patients treated with NAC on day 3 (P < 0.05). Left ventricular diastolic parameters were not different whether patients were treated with NAC or not. No difference in reduction of infarct size was detected between the groups according to CK-MB levels. It was thus demonstrated that administration of NAC in combination with streptokinase significantly diminished oxidative stress and improved LV function in patients with acute MI. These encouraging results would justify the performance of a larger controlled study.

Effects of red wine consumption on serum paraoxonase/arylesterase activities and on lipoprotein oxidizability in healthy-men

Although there is a general consensus concerning the lower risk for cardiovascular disease in moderate drinkers, the mechanisms responsible for the cardioprotective effect of red wine remain unknown. It has been proposed that increased serum paraoxonase activity may be a mechanism of action underlying reduced cardiovascular disease risk in moderate drinkers, since paraoxonase inhibits lipoprotein oxidation. The aim of this study was to investigate the effects of red wine consumption on serum paraoxonase/arylesterase activities and on lipoprotein oxidizability in healthy-men. Fourteen healthy-men were included in the study. The subjects consumed 0.375 g alcohol / kg body weight for 3 weeks. Paraoxonase and arylesterase activities were studied spectrophotometrically. Oxidizability of apolipoprotein B-containing lipoproteins were determined, after separating them with precipitation method, by incubating with copper-sulfate. Paraoxonase activity did not change, however arylesterase activity significantly decreased after red wine consumption (P < 0.01). There was a reduced susceptibility of apolipoprotein B-containing lipoproteins to copper-sulfate induced oxidation after red wine consumption (P < 0.01). Our results support that red wine protects lipoproteins against oxidation, however there was not any significant change in serum paraoxonase activity after red wine consumption.

The relation between oxidant and antioxidant parameters and severity of acute coronary syndromes.

Objective — Acute coronary syndromes (ACS) encompass a continuum of cardiac ischaemic events, ranging from unstable angina pectoris (UA) to ST-segment elevation myocardial infarction (STEMI). Oxidative stress may play an important role in the pathogenesis of acute coronary diseases. In the present study, we examined the associations between lipid and protein susceptibility to oxidation and total sialic acid (SA) and antioxidant status and the severity of ACS as determined by having UA, non-STEMI or STEMI. Methods and results — The study sample consisted of 102 patients with ACS and 45 controls. Malondialdehyde (MDA) as a marker of lipid peroxidation and protein carbonyls as a marker of protein oxidation were measured to show the susceptibility to oxidation.Antioxidant status was determined by measuring the carotenoids, vitamin C and vitamin E levels and paraoxonase and arylesterase activities. In addition to conventional lipid and lipoprotein analysis, MDA and vitamin E were quantitated by high-performance liquid chromatography.Total SA and other oxidant and antioxidant parameters were studied spectrophotometrically.As expected, patients had significantly higher total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, lipoprotein (a), apolipoprotein (apo) B values and lower high-density lipoprotein cholesterol and apoAI values than controls. Our results demonstrated significant increases both in total SA levels and in indicators of oxidative stress in patients with ACS compared with the controls. However, antioxidant parameters were decreased in patients with ACS. When the patients were divided into groups with UA, non-STEMI and STEMI, respectively, total SA and oxidant parameters were significantly increased and antioxidant parameters were significantly decreased in going from UA to STEMI. Conclusions — Our study shows gradually increased lipid and protein oxidation and total SA and gradually decreased antioxidant status when the conditions advance from UA to STEMI.These results indicate that these markers may be useful both in understanding plaque destabilization and in determination of risk stratification of patients. Also, measurement of these markers may provide a noninvasive window to study atherosclerotic lesions.

Effects of different resuscitation fluids on tissue blood flow and oxidant injury in experimental rhabdomyolysis.

Objective:This study was performed to evaluate the effects of 0.9% saline (SAL), 0.9% saline + sodium bicarbonate + mannitol (SAL/BIC/MAN), and hypertonic saline-dextran (HSD) on hemodynamic variables, tissue blood flow, and oxidant injuries in experimental traumatic rhabdomyolysis (TR) in rats subjected allogeneic muscle extract infusion. Design:Prospective, randomized, experimental. Setting:Physiology experiment laboratory. Subjects:Male Sprague-Dawley rats, weighing 250–300 g. Interventions:All groups (n = 8 each) underwent femoral artery and vein catheterization. The animals in the TR, SAL, SAL/BIC/MAN, and HSD groups received an infusion of 2 mL of autologous muscle extract for 60 mins. After autologous muscle extract infusion, the SAL and HSD groups received 30 mL/kg 0.9% saline for 30 mins or 4 mL/kg HSD for 5 mins, respectively. The SAL/BIC/MAN group received 30 mL/kg 0.9% saline for 30 mins plus a bolus of 1 g/kg mannitol and a bolus of 2 mEq/kg sodium bicarbonate diluted in 1 mL of saline. At 2 hrs of autologous muscle extract infusion, erythrocyte flows in liver and kidney were measured by using a laser Doppler flowmeter. Then, blood samples and kidney and liver biopsies were taken to measure levels of glutathione and malondialdehyde. Measurements and Main Results:TR caused decreases in mean arterial pressure, tissue blood flow, and tissue glutathione and an increase in malondialdehyde. Rats in the HSD group had significant metabolic acidosis. SAL resuscitation did not correct tissue blood flow and prevent oxidant injury. HSD increased tissue blood flow, mean arterial pressure, and liver and kidney glutathione and decreased serum, liver, and kidney malondialdehyde. SAL/BIC/MAN resuscitation corrected all oxidant damage variables but did not increase tissue blood flow. SAL/BIC/MAN preserved serum malondialdehyde and liver glutathione better than the HSD did. Conclusions:HSD prevented oxidant injury and restored tissue blood flow but increased metabolic acidosis that followed autologous muscle extract infusion. SAL/BIC/MAN seems to be more effective than HSD in decreasing oxidant injury. Further research on the effects of the solute overload and metabolic acidosis due to HSD resuscitation on renal function in experimental rhabdomyolysis is warranted.

Hypertonic saline dextran alleviates hepatic injury in hypovolemic rats undergoing porta hepatis occlusion.

To monitor the ischemic and/or reperfusion injury after porta hepatis occlusion (Pringle maneuver) in livers subjected to hypotension, serum alanine amino transferase (ALT), liver malondialdehyde (MDA), and liver glutathione (GSH) levels were measured. MDA is a by-product of oxidant-induced lipid peroxidation, and GSH is an endogenous antioxidant. The effects of lactated Ringers (LR) and hypertonic saline (7.5%)/Dextran (6%; HSD) resuscitation on liver injury, if any, was investigated. Rats in sham (S, n = 8) and five other groups (n = 8) underwent femoral artery and vein catheterization and laparotomy. The hemorrhage and ischemia (HI) group was bled 30% of their blood volume and had their porta hepatis occluded for 30 min. The HI, LR, and HSD groups underwent both hemorrhage and occlusion. Thirty minutes after hemorrhage, the LR and HSD groups received either LR (equivalent to three times the shed blood) or HSD (10 mL/kg) resuscitation over 30 min. Both LR and HSD resuscitation lowered the increased ALT and liver tissue MDA seen in the HI group. ALT was decreased from 348 ± 93 IU/L in the HI group to 200 ± 98 IU/L in the LR and 139 ± 74 IU/L in the HSD groups. Liver tissue MDA was 353 ± 22 nmol/g/tissue in the HI group and LR decreased it to 261 ± 17 nmol/g/tissue, whereas HSD decreased it to 273 ± 20 nmol/g/tissue. The decrease in ALT and the increase in liver GSH were more pronounced with HSD resuscitation (P < 0.05). HSD seems to be more effective than LR in decreasing the liver tissue damage produced by total hepatic inflow occlusion under hypovolemic conditions.

Effective inhibition of cardiomyocyte apoptosis through the combination of trimetazidine and N-acetylcysteine in a rat model of myocardial ischemia and reperfusion injury

OBJECTIVE Apoptosis is the early and predominant form of cell death in infarcted myocardia. The aim of the study was to investigate the effects of trimetazidine (TMZ) and N-acetylcysteine (NAC), used alone or in combination, on oxidative stress, infarct size, and ischemia-reperfusion (IR)-induced cardiomyocyte apoptosis in a rat model of myocardial IR. METHODS AND RESULTS Myocardial IR was established by ligating an area under the left main coronary artery for 30 min followed by 3 h of reperfusion. Saline (1 ml/kg), NAC (50, 150 mg/kg), or TMZ (3, 5 mg/kg) was intravenously injected during the middle of the ischemic period. At the end of the reperfusion, blood samples were collected from the animals to measure serum M30 and M65 levels, which are markers of cell death, the S100b level, which is a marker of inflammation, and the malondialdehyde (MDA) level, which is a marker of oxidative stress. The infarct size was evaluated as the ratio of the infarct area to the risk area. Apoptotic activation was assessed by caspase-3 immunostaining and a TUNEL assay. TMZ and NAC, either alone or in combination, significantly reduced serum MDA levels, infarct area and apoptotic activity compared to those observed in saline group. Interestingly, the infarct area was more smaller in TMZ (3 and 5 mg/kg) injected groups (9.72 ± 1.3% and 9.96 ± 2.3%) than those observed in NAC (50 and 150 mg/kg) (16.1 ± 2.5% and 19.1 ± 2.14%) or TMZ (5 mg/kg)- NAC (150 mg/kg) combination groups (16.9 ± 1.6%). However, the apoptotic activity was reduced more significantly in the combination of TMZ (5 mg/kg)-NAC (50 mg/kg) compared to TMZ-only group. Neither TMZ or NAC treatments nor the combination of the drugs significantly affected serum M30, M65 and S100B levels. CONCLUSION Intravenous NAC and TMZ administration decreased oxidative stress, infarct area and apoptotic activity in a rat model of IR. Although the combination treatment was more effective in reducing the apoptotic activity than either treatment groups alone, TMZ treatment was more successful in reducing the infarct area than NAC or combination treatments. Present results suggest that, in addition to mechanical attempts to secure myocardial reperfusion, the use of TMZ and NAC may help to reduce IR injury.

Oxidizability of apolipoprotein B-containing lipoproteins, levels of lipid peroxidation products and antioxidants in normal pregnancy

ObjectThe object was to assess oxidizability of apolipoprotein B-containing lipoproteins, levels of lipid peroxidation products and antioxidants in normal pregnancy.MethodSerum malondialdehyde, vitamin E, carotenoids, albumin, uric acid, bilirubin, triglyceride, total cholesterol levels and in vitro copper-induced oxidation of apolipoprotein B-containing lipoproteins were investigated in 21 healthy pregnant and 22 nonpregnant women. Mann-Whitney U test was used for the statistical analyses.ResultsSerum malondialdehyde, vitamin E, triglyceride and total cholesterol levels were significantly higher; albumin and uric acid levels and vitamin E/triglyceride + total cholesterol and carotenoids/triglyceride + total cholesterol ratios were significantly lower in the pregnant group. Basal malondialdehyde concentrations of apolipoprotein B-containing lipoprotein fraction and Δ-malondialdehyde values determined at 30, 60, 90, 120, 150 and 180th minutes of incubation were significantly lower in the pregnant group compared to those in the non-pregnant group.ConclusionAlthough greater lipid peroxidation product levels reflect an enhanced lipid peroxidation status in normal pregnancy, apolipoprotein B-containing lipoprotein fraction of normal pregnant women compared with the nonpregnant subjects seems to be protected from oxidation.

The relationship of serum ferritin with malondialdehyde concentration in patients with coronary artery disease: Ferritin and oxidative stress in CAD

It has been suggested that the risk of coronary heart disease increased with increasing body iron stores. Free iron catalyzes the generation of free radicals and free radicals promote the oxidation of lipids. The aim of this study was to determine the association of serum ferritin levels with coronary artery disease (CAD) and to establish the relation of ferritin to the lipid peroxidation product malondialdehyde (MDA). The study included 188 patients. Thirty-eight patients (mean age: 55±9 years) had angiographically normal coronary arteries and 150 patients (mean age: 54±10 years) had significant stenosis at least in one coronary artery. Serum ferritin, total iron binding capacity (TIBC), MDA levels, lipoprotein variables and CAD risk factors were determined in all patients. Serum ferritin levels were significantly higher in patients with CAD compared with control groups (105±65 ng/ml versus 83±71 ng/ml) (p<0.01). TIBC was lower in patients with CAD (333±62 µg/dl) versus 348±48 µg/dl), (p<0.05). In patients with CAD, serum MDA levels were significantly higher when compared with control groups (8.1±2 nmol/ml versus 5.9±1.8 nmol/ml), (p<0.001). There were positive correlation between ferritin and MDA levels (r=0.20, p=0.02) and negative correlation between TIBC and MDA levels (r=0.22, p=0.001). These findings support the concept that iron, being an important transition metal, might contribute to atherogenesis, along with the classic risk factors. The results are also in agreement with the concept that iron overload would elevate the risk of CAD by promoting the lipid peroxidation.