Bolkan Şimşek

Plasma total homocysteine and cysteine levels as cardiovascular risk factors in coronary heart disease

OBJECTIVES As an important risk factor for coronary atherosclerosis, elevated plasma total homocysteine (t-hcy) concentration has recently received greater attention than have conventional risk factors. Though less reactive than homocysteine, cysteine (cys) is the most abundant plasma thiol and may function as an extracellular regulating factor of thiol/disulfide exchange in order to maintain an adequate redox status. An increase in the total amount of this compound may be noxious depending on environmental conditions. In the present study, the aim was to investigate changes of plasma total cysteine, homocysteine and other determinants in different types of coronary heart disease. DESIGN AND METHODS Plasma total homocysteine (t-hcy), cysteine (t-cys), cysteinylglycine (t-cysgly), folic acid, vitamin B(12), lipid parameters, total protein, albumin and creatinine levels were studied in plasma from 68 patients with coronary heart disease and 42 healthy controls. After reduction of disulfide bonds with tri-n-buthylphosphine, plasma total thiols were assayed using high performance liquid chromatography (HPLC) and fluorescence detection following derivatization of sulfhydryl groups with 7-fluoro-benzo-2-oxa-1,3-diazole-4-sulfonate (SBD-F). Other parameters were determined by using commercial kits. RESULTS Plasma t-hcy and t-cys levels were higher in patients (P<0.0001) than in controls, but t-cysgly was unchanged. Hcy and cys levels were correlated with age in the whole study population (r=0.49, r=0.46, P<0.01). Plasma t-hcy positively correlated with plasma t-cys (r=0.53, P<0.01) and t-cysgly (r=0.49, P<0.01) in patients, and with plasma t-cys (r=0.57, P<0.01) in controls. Postmenopausal women had higher t-cys and t-hcy levels than premenopausal women among the controls (P<0.01). Folate and vitamin B(12) levels were similar in both patients and controls. Patients with vitamin B(12) levels below normal had higher plasma t-cys and t-cysgly levels (P<0.05). Interestingly, control subjects with lower vitamin B(12) levels had lower plasma t-hcy levels (P<0.05). Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, total protein, albumin and creatinine levels in patients and controls were within the normal range, but only HDL-cholesterol levels in patients were lower than in controls (P<0.0001). Triglyceride and VLDL levels of patients were also higher than those of controls (P<0.0001). CONCLUSIONS Higher plasma total cysteine levels are as important as higher plasma total homocysteine levels. Both parameters are intercorrelated and may act synergistically. To discern their respective roles in atherosclerotic disease, these aminothiol levels have to be considered together.

Lipid peroxidation and antioxidant status in blood and tissue of malignant breast tumor and benign breast disease

Changes in the levels of malondialdehyde (MDA), nitrate and nitrite (as an index of nitric oxide production), lipid hydroperoxide (LOH), total antioxidant capacity (TAC), lipids (total cholesterol and triglycerides) and lipoproteins (HDL‐ and LDL‐cholesterol) were estimated in breast cancer patients (n = 15) and benign breast disease (n = 15). Serum and tissue MDA levels were found to be decreased in breast cancer patients compared to the benign group (p < 0.05). In contrast, nitrate and nitrite levels were increased in serum and tissue of the cancer group compared to benign breast disease patients (p < 0.05). Compared to the benign group, tissue TAC levels were elevated in the breast cancer patient group (p < 0.05). Total cholesterol and HDL‐cholesterol were elevated in the benign group compared with cancer patients (p < 0.05). These findings support the hypothesis that lipid peroxidation in serum and tissue of benign breast disease is greater than in breast cancer. However, the enhanced levels of nitric oxide may be in response to inflammation in patients with breast cancer. Total antioxidant status is lower in benign tissue than in cancerous tissue, probably to compensate for this elevated free radical production.

Oxidation of Uric Acid in Rheumatoid Arthritis: Is Allantoin a Marker of Oxidative Stress?

Free radicals are implicated in many diseases including atherosclerosis, cancer and also in rheumatoid arthritis. Reaction of uric acid with free radicals, such as hydroxyl radical and hypochlorous acid (HOCl) results in allantoin production. In this study, we measured the serum allantoin levels, oxidation products of uric acid, as a marker of free radical generation in rheumatoid arthritis. Fasting blood samples were obtained from 21 rheumatoid patients and 15 healthy controls. In this study, the serum allantoin and uric acid levels were measured by a gas chromatography–mass spectrometry method and the ratios were calculated. The mean allantoin and uric acid levels and ratios in the patient group were 22.1±11.3, 280.5±65.0 and 8.0±3.7 μM, while in the control group they were 13.6±6.3, 278.3±53.6 and 4.9±2.1 μM, respectively. The effects of gender, age, menopausal status, duration of disease and medications on serum allantoin and uric acid levels of the patient and control groups were studied. Our results suggest that uric acid acts as a free radical scavenger and thus is converted to allantoin. Increased allantoin levels suggest the possible involvement of free radicals in rheumatoid arthritis.

Circulating nitric oxide (NO), asymmetric dimethylarginine (ADMA), homocysteine, and oxidative status in obstructive sleep apnea–hypopnea syndrome (OSAHS)

Obstructive sleep apnea–hypopnea syndrome (OSAHS) with episodic hypoxia–reoxygenation is associated with increased cardiovascular morbidity and mortality. Therefore, increased homocysteine, asymmetric dimethylarginine (ADMA), oxidative status, and decreased nitric oxide levels have been implicated as possible mechanisms for development of cardiovascular diseases. We aimed to investigate changes in the levels of these substances in patients with OSAHS in comparison with nonapneic controls. Thirty-four OSAHS patients and 15 healthy controls were included in this study. In the blood samples, oxidative status and nitric oxide levels were measured with spectrophotometric methods. Plasma ADMA and homocysteine levels were determined by using high-performance liquid chromatography with fluorescence detection. Nitric oxide levels were significantly low in OSAHS patients (p < 0.05) and correlated with mean SaO2 (r = 0.513, p < 0.002) and lowest SaO2 (r = 0.363, p < 0.03). Oxidative status, ADMA, and homocysteine levels were higher in OSAHS patients, but difference did not reach statistical significance. After dividing patients into moderate (AHI = 5–29) and severe (AHI ≥ 30) OSAHS groups, significantly increased homocysteine levels were observed in the severe OSAHS group (p < 0.05). Nitric oxide levels negatively correlated with oxidative status in total OSAHS patients (r = −0.415, p < 0.02) and also in severe OSAHS group (r = −0.641, p < 0.007). Hyperhomocysteinemia and diminished NO production may be causal factors in endothelial dysfunction seen in OSAHS and may explain the association between OSAHS and cardiovascular diseases. These modifiable factors should be monitored in patients suspected of having OSAHS.

Assessment of homocysteine, neopterin and nitric oxide levels in Behcet's disease

Abstract Background: Behçets disease is a multysystemic immunoinflammatory disease with a wide variety of clinical manifestations, whereas recurrent aphthous stomatitis is a local oral disease. The aim of this study was to examine the distribution of homocysteine levels in patients with active Behçets disease, possible association of homocysteine with nitric oxide and neopterin levels, and to characterize the differences between patients with Behçets disease and those with recurrent aphthous stomatitis in terms of these parameters compared with healthy controls. Methods: A total of 23 patients with active Behçets disease, 25 patients with recurrent aphthous stomatitis as positive controls, and 21 healthy subjects were included in this study. Serum homocysteine and neopterin levels were measured flourimetrically by HPLC. Serum nitric oxide production was assayed by measuring total nitrite levels with Griess reagent. Results: Significantly higher homocysteine (12.9±3.3 μmol/L) and lower nitric oxide (41.5±10.9 μmol/L) and neopterin (6.4±1.0 nmol/L) levels were observed in patients with Behçets disease compared with healthy controls (10.7±2.0 μmol/L, 49.7±16.2 μmol/L, 8.7±2.2 nmol/L, respectively) (p<0.03 for neopterin, p<0.04 for homocysteine and nitric oxide). However, homocysteine, nitric oxide, biopterin and neopterin levels and the neopterin/biopterin ratio for recurrent aphthous stomatitis patients were not significantly different compared to healthy controls. A significant positive correlation was observed between serum homocysteine and serum neopterin/biopterin ratio in patients with Behçets disease (r=0.975, p<0.005). Conclusions: In contrast to recurrent aphthous stomatitis, there is a higher prevalence of hyperhomocysteinemia in Behcets disease. Homocysteine may have deleterious effects on the pathology of Behcets disease by decreasing nitric oxide levels and interfering with the immune system. Clin Chem Lab Med 2007;45:73–7.

Evaluation of allantoin levels as a new marker of oxidative stress in Behçet's disease.

The increased production of reactive oxygen species (ROS) from activated neutrophils in Behçets disease (BD) and recurrent aphthous stomatitis (RAS) may result in increased oxidative stress. Uric acid can react rapidly with neutrophil‐derived ROS to form allantoin. The purpose of the study was to evaluate the serum levels of allantoin as a new marker of oxidative stress in BD compared with malondialdehyde (MDA) levels as a well‐known marker. Blood samples were obtained from 23 BD patients, 22 RAS patients as positive controls, and 21 healthy controls. When compared to the healthy controls, we found higher allantoin and MDA levels in the BD patients and higher MDA levels in the RAS patients. Serum ascorbic acid levels in the BD patients were significantly lower than in the controls. Increased allantoin and MDA levels suggest the possible involvement of free radicals in BD. As allantoin is only a product of uric acid oxidation by reactive oxygen and nitrogen species, it may also be used as a marker of oxidative stress in BD.

Ascorbic acid and uric acid levels in lung cancer patients

Objective: To study any possible association between serum ascorbic acid and uric acid levels with lung cancer.

The association between total antioxidant status and oxidative stress in Behçet's disease.

There has recently been growing evidence supporting the importance of oxidative stress in the pathogenesis of Behçet’s disease (BD). In this study, we aim to evaluate total antioxidant status (TAS) and total oxidative stress (TOS) in BD patients, and compare their results both with controls that had recurrent aphthous stomatitis (RAS) and healthy controls. TAS statistically decreased in RAS patients, and TOS levels increased in BD and RAS patients than those in healthy controls. The serum levels of Cu significantly increased only in BD patients when compared with healthy controls. Fe levels were not statistically different among the BD patients, RAS patients and healthy controls, but there was a positive correlation between TOS and plasma Fe levels in BD patients. Our results suggest that there is an insufficient antioxidant system and increased oxidative status both in BD and RAS patients. The antioxidant supplementations in addition to medical treatments will improve the quality of life.

Increased oxidative DNA damage and impaired antioxidant defense system in patients with gastrointestinal cancer

BACKGROUND Highly active intermediates are formed in aerobic metabolism which in turn leads to cellular damage. It is increasingly proposed that free radicals play a key role in human cancer development. The aim of this study was to investigate changes in 8-hydroxy-deoxyguanosine, nitrite+nitrate, total glutathione, total antioxidant capacity levels and superoxide dismutase, catalase, glutathione peroxidase activities in operative patients with gastrointestinal cancer before and after surgery and compare with inoperative patients. METHODS Oxidative stress parameters were measured in 59 gastrointestinal cancer patients and 20 controls. 8-hydroxy-deoxyguanosine was quantitated by Elisa method. Superoxide dismutase, catalase, glutathione peroxidase were assayed with colorimetric methods; Nitrite+nitrate, total glutathione and total antioxidant capacity were assayed with spectrophotometric methods. RESULTS 8-hydroxy-deoxyguanosine levels in cancer patients were higher than those of control group (p<0.01). Similarly, glutathione levels were increased compared with controls (p<0.01). However, nitrite+nitrate, total antioxidant capacity levels and superoxide dismutase and catalase activities were decreased in cancer patients compared with controls (p<0.01, p<0.01, p<0.05, p<0.01, respectively). The patients were divided into two groups; operative (n = 30) and inoperative (n = 29). A significant difference was found in inoperative group compared with postoperative group according to glutathione peroxidase activity (p<0.05). DISCUSSION Our results demonstrate that the oxidant/antioxidant balance was altered in favor of free radicals and DNA damage in gastrointestinal cancer patients. Significant increases in 8-hydroxy-deoxyguanosine, glutathione and decreases in nitrite+nitrate, SOD, CAT activities and antioxidant molecules suggest the possible involvement of oxidative stress in gastrointestinal cancer. Glutathione peroxidase activities in postoperative patients were higher compared to inoperative patients.

Variability of total thiol compounds, oxidative and nitrosative stress in uncomplicated pregnant women and nonpregnant women

PurposeThe objective of this study was to determine the changes in total plasma thiols (homocysteine, cysteine and cysteinylglycine), lipid peroxidation and nitric oxide concentrations during normal pregnancy.MethodsThese variables were measured in 28 uncomplicated pregnant women at first, second and third trimesters and in 19 nonpregnant women.ResultsThe mean concentrations of homocysteine, cysteine and cysteinylglycine were significantly lower in all trimesters of pregnancy compared with nonpregnant controls. There was significant elevation in serum lipid peroxidation levels of pregnant women within first and third trimesters compared with nonpregnant women. In spite of increase in mean nitric oxide levels in pregnant women, this increase did not reach statistically significant levels.ConclusionThis study provides information about the changes in plasma levels of many variables having important role in pregnancy complication during all trimesters in uncomplicated pregnancy compared with nonpregnant women.