Effects of thiamine treatment on oxidative stress in experimental diabetes.

AIM: Hyperglycemia, oxidative stress and hyperlipidemia are features of diabetes mellitus. Thiamine has beneficial effects on carbohydrate metabolism and it was proposed that this vitamin has antihyperlipidemic and antioxidant effects. Our aim was to investigate the effects of thiamine on oxidative stress and metabolic changes in streptozotocin (STZ) induced diabetic rats. METHOD: Diabetes was induced by a single intraperitoneal injection of STZ. Thiamine (6 mg/kg) was added to drinking water for five weeks. The rats were divided into four groups: control rats; thiamine treated control rats; diabetic rats; thiamine treated diabetic rats. Plasma and tissue malondialdehyde (MDA) levels were measured by high-performance liquid chromatography and spectrophotometry, respectively. Paraoxonase (PON) and arylesterase (AE) activities were measured with spectrophotometric methods, and erythrocyte superoxide dismutase (SOD) and blood glutathione peroxidase (GSH-Px) activities were determined using commercial kits. RESULTS: Thiamine treatment reduced plasma and tissue MDA levels, serum glucose, total cholesterol and triglyceride levels, and increased serum high density lipoprotein- cholesterol and insulin levels, serum PON and AE, erythrocyte SOD and blood GSH-Px activities. CONCLUSION: Thiamine significantly improves oxidative stress and has hyperinsulinemic and antihyperlipidemic effects so we suggest that thiamine might be used as a supportive therapeutic agent in diabetes (Tab. 2, Fig. 3, Ref. 53).

SHORT TERM EFFECT OF LAPAROSCOPIC SLEEVE GASTRECTOMY ON CLINICAL, RENAL PARAMETERS AND URINARY NGAL LEVELS IN DIABETIC AND NON DIABETIC OBESITY.

BACKGROUND: Although diseases such as diabetes, hypertension, obstructive sleep apnea and hyperlipidemia are clearly documented as obesity associated diseases, it is not well-known whether obesity causes renal pathologies. The aim of the present study was to evaluate the effect of weight loss following laparoscopic sleeve gastrectomy on clinical, renal parameters and urinary Neutrophil gelatinase-associated lipocalin (NGAL) levels in diabetic and non-diabetic obese patients. METHODS: Nineteen morbidly obese patients (10 diabetic and 9 non diabetic) who underwent laparoscopic sleeve gastrectomy were evaluated clinically (anthropometric measurements) and biochemically before surgery and at 6 months from surgery. RESULTS: Significant decreases in weight, BMI, FPG, PPG and HbA1c levels were observed in the diabetic group when the baseline and 6th month parameters of the patients were compared. There was also a significant decrease in SBP and DBP. At 6th month following laparoscopic sleeve gastrectomy, renal parameters such as creatinine, mAlb/creatinine, NGAL/creatinine did not differ in the diabetic group. In the nondiabetic group, serum creatinine levels were significantly decreased, but other renal parameters such as mAlb/creatinine and NGAL/creatinine were not significantly different. CONCLUSIONS: Our findings revealed significant decreases in weight, body mass index and glycemic parameters after sleeve gastrectomy in diabetic and non-diabetic patients, while no significant alteration was noted in renal functions, urinary NGAL and microalbumin levels.

Fluvastatin Decreases Oxidative Stress in Kidney Transplant Patients.

OBJECTIVE: Oxidative stress has been suggested to have a pivotal role in the development of cardiovascular disease in kidney transplant patients (KTPs). The effects of fluvastatin on oxidative status in KTPs have not been well evaluated. The aim of the present study was to evaluate the effects of fluvastatin on oxidative status by investigating erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPx), serum paraoxonase (PON1), and serum arylesterase (ARE), along with lipid peroxidation products, serum malonldialdehyde, and apolipoprotein B malondialdehyde (ApoB MDA). METHODS: Eighteen KTPs were included in the present study. Blood samples were obtained after 1 night's fast. Erythrocyte SOD, erythrocyte GPx, serum PON1, serum ARE, serum MDA, and ApoB MDA were measured using methods described previously. Paired-sample t test was used for comparing the changes from week 0 to week 4 of parameters that might be associated with fluvastatin treatment. RESULTS: The present study has shown that erythrocyte SOD and GPx, and serum PON1 and ARE activities increased at the fourth week of the statin treatment. Furthermore an increase in the antioxidant enzymes following fluvastatin may be a clue for the antioxidant effects of this drug. Four weeks of fluvastatin long-acting tablets 80 mg/day led to a decrease in plasma Apo-MDA and MDA levels. CONCLUSION: The findings of the present study demonstrate that fluvastatin 80 mg long-acting tablets may be used safely for 4 weeks and decrease atherogenic lipoproteins in KTPs. Furthermore, after 4 weeks of fluvastatin treatment, the levels of antioxidant parameters increased and oxidative parameters decreased. Further placebo-controlled treatment studies would be helpful to evaluate the effects of fluvastatin on oxidant and antioxidant parameters including PON1 in patients with KT.

Baseline and salt-stimulated paraoxonase and arylesterase activities in patients with chronic liver disease: relation to disease severity.

BACKGROUND: It has been recently reported that serum paraoxonase (PON1) and arylesterase (ARE) activities may be significantly reduced in patients with chronic liver disease. The aim of the study was to investigate the relations between serum PON1 and ARE activities and the degree of liver damage in patients with chronic liver injury. METHODS: We studied a total of 75 patients with chronic liver disease (50 patients with cirrhosis and 25 patients with chronic hepatitis) and 25 healthy comparison subjects. Baseline and salt-stimulated PON1 and ARE activities were determined in all study participants. RESULTS: Baseline and stimulated PON1 and ARE activities were significantly lower in patients with chronic liver disease than in controls. Cirrhotic patients in Child-Pugh classes B and C subgroups had significantly reduced PON1 and ARE activities compared with Child-Pugh class A patients (both P-values <0.01). Receiver operating characteristic curve analysis showed that serum ARE activity was the most efficient test for identifying the presence and severity of chronic liver injury. CONCLUSION: Baseline and stimulated PON1 and ARE activities are reduced in patients with chronic liver disease. Serum ARE activity could be a suitable biomarker for the evaluation of the presence and severity of chronic liver damage.

Oxidative status and prevalent cardiovascular disease in patients with chronic renal failure treated by hemodialysis.

BACKGROUND: Hemodialysis (HD) patients are exposed to oxidative stress which contributes to cardiovascular disease (CVD). The purpose of this study was to investigate the oxidative and antioxidative status in HD patients with (CVD+, n = 38) and without (CVD-, n = 67) prevalent CVD. PATIENTS AND METHODS: A total of 105 HD patients and 21 healthy controls were assessed for lipid peroxidation indices (plasma malondialdehyde (MDA)), oxidizability of apolipoprotein B-containing lipoproteins (apo B-deltaMDA) and red blood cells (RBC-MDA) together with various components of the antioxidant system in plasma (paraoxonase/arylesterase activities, total carotenoids, vitamins C and E) and RBC (superoxide dismutase and glutathione peroxidase activities). RESULTS: Plasma MDA and RBC-MDA were significantly higher, vitamin C and total carotenoid levels were significantly lower in both CVD+ and CVD- HD groups than in the control group. Plasma MDA levels were significantly higher and serum paraoxonase activity, uric acid and albumin levels were significantly lower in patients with CVD+ HD patients compared to those of the CVD- patients. CONCLUSION: This study suggests that the elevated level of plasma MDA and the lower activity of paraoxonase could contribute to the increased incidence of cardiovascular disease in hemodialysis 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 Student's 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.

Exercise-induced oxidative stress and muscle performance in healthy women: role of vitamin E supplementation and endogenous oestradiol.

The purpose of this study was to investigate the individual and combined antioxidant effects of menstrual cycle phase-related alterations in blood serum oestradiol concentrations and of dietary vitamin E supplementation on exercise-induced oxidative stress and muscle performance. A group of 18 sedentary women, aged 19-35 years, were given supplements of 300 mg alpha-tocopherol (n = 10) or placebo (n = 8) daily during the course of two menstrual cycles. The subjects exercised the knee isokinetically to exhaustion after cycling submaximally at 50% maximal oxygen uptake during the menstrual and preovulatory phases of their menstrual cycles. Blood samples were taken before and after the exercise, to evaluate haematocrit, plasma lactic acid and malondialdehyde concentrations, erythrocyte antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and apolipoprotein B containing lipoprotein (non-high density lipoprotein, HDL, fraction) oxidation. Serum vitamin E, follicle stimulating hormone, luteinizing hormone and oestradiol concentrations were measured in pre-exercise blood samples. Neither vitamin E supplementation nor oestradiol concentrations influenced SOD and GPx activities or the susceptibility of the non-HDL fraction to oxidation while at rest. Plasma malondialdehyde concentration was unaffected by exercise, however significant reductions in erythrocyte SOD and GPx activities and increased susceptibility of the non-HDL fraction to oxidation were noted after exercise. Exercise-induced changes were reduced when oestradiol concentration was high in the preovulatory phase, independent of the serum vitamin E concentrations. In addition, both pre- (r = 0.58, P < 0.05) and post-exercise (r = 0.73, P < 0.001) GPx activities in placebo administered subjects were positively correlated with oestradiol concentrations. In conclusion, these findings suggest a better protective role of oestradiol against oxidative injury, compared to vitamin E. Exhausting muscle performance was, however, not influenced by vitamin E supplementation and/or cycle-phase related changes in oestradiol concentrations.

Relation of functional capacity with the oxidative stress and antioxidants in chronic heart failure.

Chronic heart failure is a common, disabling disorder with high mortality. Oxidative stress may have both functional and structural effects on the myocardium, leading to myocardial decompensation. In this study, the authors examined the relationship of oxidative stress and functional capacity in patients with varying degrees of heart failure. Fifty-one patients with chronic heart failure and 31 control subjects were studied. The functional capacity of patients was determined. Plasma malondialdehyde, vitamin E, and beta-carotene levels were measured. The malondialdehyde levels were significantly different between control subjects and heart failure patients (p=0.03). There was a positive correlation between patients' malondialdehyde levels and New York Heart Association functional class (r=0.59; p<0.0001). There was a negative correlation between the functional class and vitamin E and beta-carotene levels (r=20.43; p<0.0001 and r=20.25; p<0.01, respectively). These data demonstrate that oxidative stress is increased systemically in patients with chronic heart failure. It seems that this increase correlates with functional class. (c)2001 CHF, Inc.

Susceptibility of apolipoprotein B-containing lipoproteins to oxidation and antioxidant status in acute coronary syndromes.

BACKGROUND: Oxidized lipoproteins may play an important role in the pathogenesis of atherosclerosis, and it has been shown that antioxidants have a protective effect against the progression of atherosclerosis. HYPOTHESIS: The aim of this study was to investigate the oxidative susceptibility of apolipoprotein B-containing lipoproteins and antioxidant status in patients with acute coronary syndromes and chronic stable angina pectoris. METHODS: The study population included 70 patients with acute coronary syndromes (14 with recent acute myocardial infarction and 56 with unstable angina pectoris), 105 patients with stable angina pectoris, and 75 control subjects. In addition to conventional lipid and lipoprotein analysis, the susceptibility of apolipoprotein B-containing lipoproteins to in vitro oxidation (lag phase) and plasma vitamin E and total carotene levels was measured. RESULTS: The lag phase was significantly shorter in patients with acute coronary syndromes (45 +/- 12 min) than in patients with stable angina pectoris (51 +/- 10 min) and in control subjects (58 +/- 9 min) (p < 0.0001). Both plasma vitamin E and total carotene levels were lowest in patients with acute coronary syndromes (1.11 +/- 0.32 mg/dl and 119 +/- 32 micrograms/dl, respectively), followed by patients with stable angina pectoris (1.25 +/- 0.37 mg/dl and 132 +/- 37 micrograms/dl) and then controls (1.52 +/- 0.31 mg/dl and 167 +/- 41 micrograms/dl). CONCLUSIONS: These data suggest that there is an intense oxidative process and a lower antioxidant status in acute coronary syndromes. This may lead to plaque instability due to the activation of the inflammatory response in coronary atherosclerotic lesions.

Relation between lipoprotein (a) and in vitro oxidation of apolipoprotein B-containing lipoproteins.

OBJECTIVES: To assess the relationship between lipoprotein (a) [Lp (a)] and lipoprotein oxidation in patients with coronary artery disease (CAD). DESIGN AND METHODS: Oxidation of apolipoprotein (apo)B-containing lipoproteins, vitamin E, carotenoids, lipid-lipoprotein levels were determined in 171 CAD and 70 non-CAD subjects. RESULTS: In CAD patients with Lp (a) concentrations >/= 30 mg/dL; total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), and apo B levels were significantly higher and lag-time and age were significantly lower than those of CAD patients with Lp (a) concentrations < 30 mg/dL. In non-CAD subjects with Lp (a) concentrations >/= 30 mg/dL; TC, LDL-C, and vitamin E levels were significantly higher and lag-time was significantly lower than those of non-CAD subjects with Lp (a) concentrations < 30 mg/dL. In CAD patients, Lp (a) correlated negatively with lag-time and positively with MDA levels. Lp (a) correlated negatively with lag-time and vitamin E levels in non-CAD subjects. CONCLUSIONS: We have shown that plasma apo B-containing lipoproteins of both CAD and non-CAD subjects with Lp (a) levels >/= 30 mg/dL are more susceptible to in vitro oxidative modification than those of subjects with Lp (a) levels < 30 mg/dL. The relationship between Lp (a) and enhanced susceptibility of apo B-containing lipoproteins to oxidation, appears to support routine investigation of Lp (a).

Effects of vitamin E and vitamin C supplementation on plasma lipid peroxidation and on oxidation of apolipoprotein B-containing lipoproteins in experimental hyperthyroidism.

Increasing numbers of experimental and epidemiological studies suggest the involvement of free radicals in the pathogenesis of various disease entities. Similarly, oxidative processes have been implicated as playing roles in the genesis of hyperthyroidism-induced damage. In this study, we investigated the effects of vitamin E and vitamin C on plasma lipid peroxidation and the susceptibility of apolipoprotein B (apo B)-containing lipoproteins to oxidation in experimental hyperthyroidism. The study animals were initially divided into a control group (Group C) and a hyperthyroid group. The latter was further re-grouped later according to their vitamin supplementation status: Hyperthyroid group without vitamin supplementation (Group H), hyperthyroid group with vitamin E supplementation (Group H+E) and hyperthyroid group with vitamin C supplementation (Group H+C). Malondialdehyde (MDA) level was measured as an indicator of plasma lipid peroxidation. The apo B-containing lipoproteins were separated by precipitation and incubated with copper sulphate. The MDA levels of this non-HDL fraction were measured prior to and after 1, 2 and 3 hours of incubation. Plasma MDA levels showed no significant differences among groups. Whereas MDA levels measured in non-HDL fraction were significantly higher in Group H than Group C. Group H+E and Group H+C had significantly lower MDA levels than Group H in all these measurements. This finding strongly indicates an increased susceptibility of apo B-containing lipoproteins to oxidation in hyperthyroidism, and that vitamin E as well as vitamin C supplementation protect these lipoproteins from copper-induced oxidation.

Effects of smoking on serum lipid and lipoprotein concentrations and lecithin: cholesterol acyltransferase activity.

Cigarette smoking is one of the major risk factors for cardiovascular disease. The mechanism responsible for this association is still unknown. We measured the activity of lecithin: cholesterol acyltransferase (LCAT), a key factor in the esterification of plasma cholesterol and reverse cholesterol transport, and the levels of lipids and apolipoproteins in the serum of 27 cigarette smoking and 31 non-smoking (control) men. We could not find any significant difference among these parameters between the groups. Serum LCAT activity was lower in smokers, but the difference was statistically nonsignificant. We also classified the two groups in respect to their serum lipid levels as hyper- and normolipidemic, we observed that normolipidemic-smokers had lower (p < 0.05) high density lipoprotein-cholesterol (HDL-C) and HDL-ester cholesterol levels compared to the normolipidemic-nonsmokers. While there were no any significant differences between hyperlipidemic-smokers and nonsmokers with respect to any of the parameters. In the end we have got the idea that smoking seems to affect HDL-C and HDL-ester cholesterol levels in the normolipidemic-smokers group, only, Also, LCAT activity tended to be lower in smokers compared to nonsmokers.

Susceptibility of non-HDL fraction to oxidation in experimental nephrotic syndrome.

Hyperlipidemia is a striking feature of nephrotic syndrome (NS) and the lipid profile seen in NS is accepted as atherogenic. Both low density lipoprotein (LDL) and very low density lipoprotein (VLDL) are apolipoprotein B-containing lipoproteins which are accepted as atherogenic. Oxidized-LDL (ox-LDL) has been suggested to play a fundamental role in atherogenesis. In this study, male Sprague-Dawley rats were made nephrotic by a single intraperitoneal injection of puromycin aminonucleoside (100 mg/kg body weight). We found significant elevation in serum triglycerides, total cholesterol, malondialdehyde, vitamin E levels and total cholesterol/vitamin E ratio and decrease in total protein and albumin levels in the NS group (n:8) compared with the control group (n:9). High density lipoprotein (HDL)-cholesterol and free fatty acid levels were not significantly different between these two groups. Apolipoprotein B-containing lipoproteins (non-HDL fraction) were separated by precipitation and amount of thiobarbituric acid-reactive substances (TBARS) of non-HDL fraction were measured after 60, 90, 120, 180 minutes of incubation with copper sulphate. TBARS levels of non-HDL fraction were significantly higher in the NS group compared with the control group at all of the time periods above. In nephrotic animals, the increased lipid peroxidation was influenced by serum lipids.