ω-3 fatty acid treatment in cardiac syndrome X: a double-blind, randomized, placebo-controlled clinical study.

OBJECTIVE: We conducted a clinical trial to examine the effect of ω-3 fatty acids in patients with cardiac syndrome X (CSX). We aimed to evaluate the potential impact of ω-3 fatty acids on endothelial function, oxidative stress, and symptom relief in the CSX. METHODS AND RESULTS: Eighteen patients with CSX were enrolled according to a double-blind, randomized, placebo-controlled design. Patients were randomized to ω-3 fatty acids (1440 mg/day, n=8) or placebo (n=10) for 4 months. We assessed plasma levels of malondialdehyde (MDA), endothelium-dependent vasodilatation [flow-mediated dilatation (FMD)], endothelium-independent vasodilatation [nitroglycerin-mediated dilatation (NMD)], and status of symptom [score with Seattle Angina Questionnaire (SAQ)] before and after the treatment. After 4 months, patients who were treated with ω-3 fatty acids showed significant increases in the FMD (from 47±48 to 104±23%, P<0.05) and NMD (from 51±53 to 93±35%, P<0.05) values, and significant decreases in the plasma MDA levels (4.4±0.86 to 3.35±0.33 µmol/l, P=0.012). SAQ scores were increased significantly in both groups (from 60±14 to 73±15%, P<0.05 placebo, from 67±10 to 81±9%, P<0.05 treatment group). NMD was correlated negatively with the plasma MDA levels. CONCLUSION: Four months of therapy with a moderate dose of ω-3 fatty acids improved the endothelial function and reduced oxidative stress in patients with CSX.

Leukocyte DNA damage in children with iron deficiency anemia: effect of iron supplementation.

Iron deficiency is frequently associated with anemia. Iron is a transition-metal ion, and it can induce free radical formation, which leads to formation of various lesions in DNA, proteins, and lipids. The aim of this study was to investigate baseline oxidative DNA damage and to clarify the role of the administration of a therapeutic dose of iron on DNA oxidation in children with iron deficiency anemia (IDA). Twenty-seven children with IDA and 20 healthy children were enrolled in the study. Leukocyte DNA damage (strand breaks and Fpg-sensitive sites) was assessed using comet assay before and after 12 weeks of daily iron administration. Before the iron administration, the frequency of DNA strand breaks in the children with IDA was found to be lower than those in the control group (P < 0.05), but there was not a significant difference for frequency of Fpg-sensitive sites. After 12 weeks of iron administration, the frequency of both DNA strand breaks and Fpg-sensitive sites were found to be increased (P < 0.01). No significant association was determined between DNA damage parameters and hemoglobin, hematocrit, serum iron, total iron binding capacity, and ferritin. In conclusion, basal level of DNA strand breaks is at a low level in children with IDA. After iron administration, DNA strand breaks and Fpg-sensitive sites, which represent oxidatively damaged DNA, increased. However, this increase was unrelated to serum level of iron and ferritin.

Circulating p53 and cytochrome c levels in acute myocardial infarction patients.

BACKGROUND: Apoptosis causes myocardiocyte loss during and after myocardial infarction. Therapeutic approaches designed to arrest apoptosis would be a significant new development in the recovery of acute myocardial infarction (AMI). In order to examine apoptotic markers in the circulation, serum levels of p53 and cytochrome c were assessed in patients with AMI. METHODS: Blood samples were taken on admission (before initiation of therapy) and on the 3rd and 7th days of hospitalization. Serum levels of p53 and cytochrome c were measured by enzyme-linked immunassay. RESULTS: The serum level of p53 was higher in AMI patients on admission compared to the control group. A time-dependent decrease was observed in the serum level of p53, but there was no significant change in the serum level of cytochrome c during therapy. CONCLUSIONS: p53, but not cytochrome c, appears to have potential as a biomarker for reporting on apoptosis following myocardial infarction.

DNA damage and glutathione level in children with asthma bronchiale: effect of antiasthmatic therapy.

When the production of reactive oxygen species (ROS) exceeds the capacity of antioxidant defences, a condition known as oxidative stress occurs and it has been implicated in many pathological conditions including asthma. Interaction of ROS with DNA may result in mutagenic oxidative base modifications such as 8-hydroxydeoxyguanosine (8-oxo-dGuo) and DNA strand breaks. Reduced glutathione (GSH) serves as a powerful antioxidant against harmful effects of ROS. The aim of this study was to describe DNA damage as level of DNA strand breaks and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites, which reflects oxidative DNA damage and GSH level in children with mild-to-moderate persistent asthma; and to examine the effect of antiasthmatic therapy on these DNA damage parameters and GSH level. Before and after 8 wk of antiasthmatic therapy blood samples were taken, DNA strand breaks and Fpg-sensitive sites in peripheral leukocytes were determined by comet assay, GSH level of whole blood was measured by spectrophotometric method. DNA strand breaks and Fpg-sensitive sites in the asthma group were found to be increased as compared with control group. GSH level in the asthma group was not significantly different from those in the control group. Levels of strand breaks, Fpg-sensitive sites and GSH were found to be decreased in the asthma group after the treatment. In conclusion, oxidative DNA damage (strand breaks and Fpg-sensitive sites) is at a high level in children with asthma. DNA damage parameters and GSH level were found to be decreased after therapy. Our findings imply that antiasthmatic therapy including glucocorticosteroids not only controls asthma but also decreases mutation risk in children with asthma bronchiale.

Serum levels of p53 and cytochrome c in subjects with type 2 diabetes and impaired glucose tolerance.

PURPOSE: To examine apoptotic markers in serum of subjects with diabetes and impaired glucose tolerance (IGT). Serum levels of p53 and cytochrome c, regulator molecules for apoptosis, were measured in subjects with type 2 diabetes, subjects with IGT and healthy controls. METHODS: Forty one subjects with type 2 diabetes, 27 with IGT and 27 healthy volunteers were included in the study. Serum level of cytochrome c and p53 were measured with competitive ELISA. RESULTS: Serum levels of p53 were lower in the group of subjects with type 2 diabetes (085+/-0.39 U/ml) than in controls (1.09+/-0.49 U/ml) (P < 0.05) and in the subjects with IGT (0.98+/-0.37 U/ml) (P < 0.05). There was no significant difference between the group with IGT and controls. Also, there was no difference for serum level of cytochrome c among the groups. In the group of subjects with type 2 diabetes, serum level of cytochrome c was mildly correlated with HbA1c (r:0.39, P < 0.05). CONCLUSION: The present study shows that the serum level of p53 is lower in the patients with type 2 diabetes than in controls or in subjects with IGT. No difference was seen among the the groups for the serum level of cytochrome c.

DNA oxidation and antioxidant status in breast cancer.

PURPOSE: : Oxidant/antioxidant balance has been suggested as an important factor for initiation and progression of cancer. The objective of this study was to determine 8-hydroxydeoxyguanosine (8-OHdG) level as a marker of oxidative DNA damage, glutathione peroxidase (G-Px), and superoxide dismutase (SOD) activities as antioxidant activity, in sera from women with breast cancer. METHODS: : Forty-nine patients with malign breast tumor were included in the study. Blood samples were collected before the surgical operation. Serum level of 8-OHdG was measured with a competitive enzyme-linked immunusorbent assay kit, SOD, and G-Px activities were measured by spectrophotometric kits. RESULTS: : 8-Hydroxydeoxyguanosine level and SOD activity were found to be increased in breast cancer group as compared with control group. Glutathione peroxidase activity in the breast cancer group was lower than those in the control group. The ratio of 8-OHdG/G-Px in breast cancer patients was found to be higher than those in the controls. There were correlations between 8-OHdG and CA19-9 (r = 0.77; P < 0.01); age and G-Px (r = -0.84; P < 0.05) in the breast cancer group. CONCLUSIONS: : Data show that serum levels of 8-OHdG and SOD activities are higher in patients with breast cancer. Glutathione peroxidase activity is lower in the breast cancer group. Increased ratio of 8-OHdG/G-Px in breast cancer patients is the evidence for impaired oxidant/ antioxidant balance in breast cancer.

Oxidative DNA damage and antioxidant defense after reperfusion in acute myocardial infarction.

PURPOSE: Myocardial damage mediated by oxidative stress during acute myocardial infarction (MI) has been suggested as an obstructive factor on recovery after an MI. 8-Hydroxydeoxyguanosine (8-OHdG) is a marker for oxidative DNA damage; superoxide dismutase (SOD) and glutathione peroxidase (G-Px) are major antioxidant enzymes. We determined changes in the plasma level of 8-OHdG and activities of SOD and G-Px in patients with MI and examined the relations between those changes and other cardiac markers. METHODS: Blood samples were taken at the beginning of the therapy, on the third day of hospitalization, and on the day patients were discharged home. Plasma level of 8-OHdG and SOD and G-Px activities were measured by enzyme-linked immunosorbent assay and spectrophotometric kits, respectively. RESULTS: 8-Hydroxydeoxyguanosine level at the beginning of the therapy was found to be decreased on the third day of therapy and on the day patients were discharged home. With respect to the treatment way, 8-OHdG level was found to be slightly decreased on the third day of therapy and then remained stable in the group treated with thrombolytic agents. However, 8-OHdG level was found to be sharply decreased on the third day of therapy in the group that underwent primary percutaneous transluminal coronary angioplasty. No significant relations were determined between those measured parameters and serum levels of cardiac markers. CONCLUSION: Although not correlated with other cardiac markers, plasma level of 8-OHdG shows a decrease after reperfusion therapy in patients with MI, and primary percutaneous transluminal coronary angioplasty seems much more effective than thrombolytic therapy for providing a low level of 8-OHdG.

Oxidative DNA damage and antioxidant activity in patients with inflammatory bowel disease.

Chronic inflammation may contribute to cancer risk through the accumulation of specific products as a result of DNA damage. Endogenous antioxidant enzymes prevent the formation of these harmful products. Oxidative DNA damage and endogenous antioxidant defense were determined in patients with inflammatory bowel disease (IBD). Plasma levels of 8-hydroxydeoxyguanosine (8-OHdG) and nitric oxide (NO) and plasma activities of glutathione peroxidase (G-Px) and superoxide dismutase (SOD) were determined in patients with IBD by ELISA and spectrophotometric assay, respectively. Plasma levels of 8-OHdG, SOD, and G-Px activity were found to be increased in the patient group compared to the control group (P < 0.02, P < 0.001, and P < 0.001, respectively), whereas NO was unchanged. 8-OHdG level was found to be weakly correlated with age, NO, and SOD. The results show increased DNA damage in patients with IBD. This may explain the increased risk of developing colon cancer in these patients.