Biochemical and Histopathological Investigation of Resveratrol, Gliclazide, and Losartan Protective Effects on Renal Damage in a Diabetic Rat Model.

OBJECTIVE: To compare the protective effects of resveratrol, gliclazide, and losartan, at biochemical and histopathological levels, on the rat kidney with experimentally induced type 1 diabetes. STUDY DESIGN: A total of 35 adult male Wistar rats were divided into control, diabetic, diabetic gliclazide, diabetic resveratrol, and diabetic losartan groups. For biochemical analysis, based on one of the kidneys, superoxide dismutase, malondialdehyde, and catalase were used for measurement. The other kidney was stained for histochemical and immunohistochemical markers and examined by light microscopy. RESULTS: Nephropathy due to diabetes was developed at the end of the third week in the diabetic group: in the glomeruli, contraction from Bowman distance, diffuse mesangial matrix increasing and tubular dilation, and cytoplasmic vacuolar changes were observed. In tubulointerstitial areas, some tubular structures, an increased expression of VEGF was observed. CONCLUSION: As a result, in diabetic rats, the effects of gliclazide, resveratrol, and losartan cure were equivalent to each other according to the parameters which were followed. Resveratrol, gliclazide, and losartan significantly protected renal glomeruli and the proximal and distal tubules.

Leptin levels and lipoprotein profiles in patients with cholelithiasis.

OBJECTIVE: To determine the relationships between serum leptin and levels of lipoprotein(a) [Lp(a)], apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) in patients with cholelithiasis. METHODS: Patients with ultrasound-confirmed cholelithiasis and controls frequency-matched for age, sex, body mass index, fasting blood glucose and haemoglobin A1c levels were recruited. Fasting blood samples from all study participants were assayed for glucose, haemoglobin A1c, total cholesterol, high density lipoprotein-cholesterol (HDL-C) and triglyceride. Serum Lp(a), ApoA-1 and ApoB levels were measured using nephelometric assays; serum leptin was measured using an enzyme-linked immunosorbent assay. RESULTS: A total of 90 patients with cholelithiasis and 50 controls were included in the study. Serum levels of leptin, Lp(a), total cholesterol, triglyceride and ApoB were significantly increased, and levels of ApoA-1 and HDL-C were significantly decreased, in patients with cholelithiasis compared with controls. Serum leptin in patients with cholelithiasis were significantly positively correlated with Lp(a) and ApoB and negatively correlated with ApoA-1. CONCLUSIONS: Patients with cholelithiasis have higher leptin levels and an altered lipoprotein profile compared with controls, with increased leptin levels being associated with increased Lp(a) and ApoB levels, and decreased ApoA-1 levels, in those with cholelithiasis.

Effect of oxidative stress on antioxidant enzyme activities, homocysteine and lipoproteins in chronic kidney disease.

BACKGROUND: Our aim was to determine the association of paraoxonase (PON1), superoxide dismutase (SOD) and catalase (CAT) activities and malondialdehyde (MDA) concentration, with lipoprotein and homocysteine (Hcy) concentrations in chronic kidney disease (CKD). METHODS: We examined 60 patients with CKD (35 men and 25 women), aged 52.7 -/+ 3.1 years, and 60 age-, sex- and body mass index (BMI)-matched control subjects. Serum PON1 activity, levels of lipoproteins, Hcy and MDA were evaluated; SOD and CAT activities in erythrocytes were also investigated. RESULTS: Levels of MDA, lipoprotein (a) (Lp(a)) and Hcy were significantly higher, while PON1 activity was lower in CKD than in controls (p<0.001). There were no significant differences between the patients and controls in the SOD and CAT activities (p>0.05). Levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) were lower in CKD than in controls (p<0.001), whereas total cholesterol (T-Chol) and triglyceride (TG) levels showed no significant difference between the groups. Levels of apolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-C) were higher in CKD than in controls (p<0.001). In CKD, PON1 activities were correlated with levels of Hcy, MDA, HDL-C, Lp(a) and ApoA-I. A significant positive correlation was found between levels of Hcy and Lp(a). CONCLUSIONS: The results of this work suggest that patients with CKD exhibit an oxidant-antioxidant imbalance which is closely related to high levels of atherosclerotic risk factors.

Potential atherogenic roles of lipids, lipoprotein(a) and lipid peroxidation in preeclampsia.

AIMS: To evaluate changes in lipid profile, serum levels of malondialdehyde (MDA) and lipoprotein(a) (Lp(a)) and placental MDA in preeclamptic women, and to evaluate the atherogenic role of these changes in the pathophysiology of pre-eclampsia. METHOD: A cross-sectional study was performed in 20 normal pregnant women, 25 women with mild preeclampsia and 28 women with severe preeclampsia in the third trimester. MDA, which is the endproduct of lipid peroxidation, was measured in placental tissue by the thiobarbituric acid (TBA) method of Ohkawa and colleagues and in serum by the TBA method of Asakawa and Matsushita. Serum lipid levels were measured by with an autoanalyzer, serum apolipoprotein (Apo) A-I and Apo B were measured by nephelometric assay and serum Lp(a) level using a nephelometric agglutination assay method. In preeclamptic and normal pregnant women, multiple comparisons between groups were performed by one-way analysis of variance supplemented with Tukey's HSD post hoc test. The association between placental and serum concentrations among groups was analyzed using the Pearson correlation test. RESULTS: Serum levels of MDA, Lp(a), total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and placental MDA were significantly higher, and high-density lipoprotein cholesterol (HDL-C) and Apo A-I levels were significantly lower, in severely preeclamptic and mildly preeclamptic women than in the normal pregnant women, but no difference was observed in Apo B among groups. Serum level of Lp(a) was positively correlated with body mass index in severely preeclamptic women (r=0.489, p=0.008). A significant positive correlation was also found between serum level of MDA and systolic blood pressure in women with severe preeclampsia (r=0.375, p=0.049). CONCLUSIONS: Our findings suggest that high Lp(a), lipid peroxidation, LDL-C and TG, and low HDL-C and Apo A-I levels, are important risk factors for atherosclerosis among preeclamptic women.

Paraoxonase, total antioxidant response, and peroxide levels in children with steroid-sensitive nephrotic syndrome.

Reactive oxygen species (ROS) are reported to play a role in inducing the proteinuria of nephrotic syndrome (NS). This study investigated paraoxonase (PON), total antioxidant response (TAR), and oxidant total peroxide together with serum proteins and lipoproteins in children with steroid-sensitive NS. The study included 40 children with steroid-sensitive NS (21 with acute-period NS in group I, 19 nonproteinuric while receiving steroids in group II) and 22 sex- and age-matched formerly nephrotic children in remission weaned from steroids (group III). The following parameters were determined: total peroxide, oxidative stress index (OSI), PON and TAR. Serum proteins and lipoproteins were also determined. Patients in the active phase of NS had significantly lower PON and TAR levels and higher OSI and total peroxide values than those in full remission; no differences were found in PON, TAR, or OSI values of groups I and II. Significant correlations were found between PON, TAR, and total peroxide. Serum total protein had a significantly positive correlation with PON and negative correlation with total peroxide in acute-period NS patients. Our results demonstrate greater oxidative stress and decreased antioxidants in the active phase of steroid-sensitive NS and while patients receive steroids than during full remission. Low-dose alternate-day steroids do not seem to decrease oxidative stress even while proteinuria ceases. Despite some conflicting data increased oxidation and/or decreased antioxidant response may be related to the pathogenesis of steroid-sensitive NS.

Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels in preeclampsia.

OBJECTIVE: To investigate the changes in enzyme activities of erythrocyte superoxide dismutase (SOD), catalase, and placental glutathione peroxidase (GSH-Px), and analyze the levels of serum malondialdehyde (MDA), copper (Cu), zinc (Zn), selenium (Se), leptin and placental MDA and glutathione (GSH). STUDY DESIGN: Cross-sectional prospective study consisting of 32 preeclamptic (PE) pregnant, 25 non-pregnant (NP) women, 28 healthy pregnant (HP) women. Levels of lipid peroxides in serum and placenta, and activities of SOD, catalase in erythrocyte and placental GSH level, placental GSH-Px activity were measured by spectrophotometric methods. Serum levels of Cu, Zn, Se measured by atomic absorption spectrophotometry. Serum levels of leptin was measured by enzyme immunoassay by using the Cayman chemical kit. One-way analysis of variance and post hoc Tukey-HSD test and Pearson correlation test were used for the statistical analyses. RESULTS: Serum levels of MDA, Cu, Leptin were markedly higher (P < 0.001); and serum level of Se was markedly lower (P < 0.001) in PE women compared with HP women and NP women. Also, placental MDA level was higher (P < 0.001) and placental GSH-Px activity was lower in PE women compared with HP women. In preeclamptic women erythrocyte catalase activity was markedly increased (P < 0.001), while erythrocyte SOD activity was markedly decreased (P < 0.001) compared to HP women and NP women. Placental GSH level was decreased compared to HP women (P < 0.001). Serum level of Zn was markedly decreased compared to NP women (P < 0.001) but no significant difference was observed in PE pregnant when compared with HP women (P > 0.05). Placental MDA level in PE women had significant negative correlation with serum Se level (r = -0.353, P < 0.05). A negative correlation was found between erythrocyte catalase activity with birth weight (r = -0.528, P < 0.001). Also, there were a significant negative correlation between serum levels of Cu and Se in the preeclamptic women (r = -0.407, P < 0.05). CONCLUSION: Our data demonstrate that elevation of lipid peroxides together with impaired antioxidant defense mechanisms and status of trace metals and the presence of possible interrelationship and crosstalk between those parameters may be related at least partly to the pathogenesis of preeclampsia. Additionally, lipid peroxides and blood oxidative imbalance could be part of the cytotoxic mechanisms leading to endothelial cell injury.

Serum leptin levels in asthmatic children treated with an inhaled corticosteroid.

BACKGROUND: Recent observations suggest the presence of an interaction between leptin and the inflammatory system; however, there is no adequate knowledge about the role of leptin in atopic states such as asthma. OBJECTIVES: To evaluate the potential role of leptin in relation to bronchial asthma and inhaled corticosteroid therapy. METHODS: Twenty-three children with mild-to-moderate, newly diagnosed asthma enrolled in this 2-period trial. The control group consisted of 20 age- and sex-matched children. Serum leptin levels were measured in patients at initiation and after 4 weeks of budesonide treatment and were compared with control group measurements. RESULTS: Asthmatic children had higher mean +/- SD serum leptin levels at admission (19.3 +/- 5.1 ng/mL) than after budesonide treatment (10.6 +/- 1.6 ng/mL) and vs control group measurements (9.8 +/- 1.6 ng/mL) (P < .001). There was a significant correlation between serum leptin levels before and after budesonide treatment (r = 0.68; P = .007). Mean +/- SD body mass indices in patients and controls were 16.7 +/- 2.1 and 16.9 +/- 2.6 kg/m2, respectively. Serum leptin levels did not correlate with body mass indices before budesonide treatment in the study group (r = -0.13; P = .65) but correlated well after budesonide treatment (r = 0.58; P = .009) and in the control group (r = 0.65; P = .008). CONCLUSIONS: The role of leptin elevation in children with asthma might be a regulatory mechanism rather than being etiologic, but a question may be raised whether it is possible that leptin may contribute to poor patient outcomes. Further research, both basic and clinical, is essential to explain the exact mechanism.

Relationship among serum selenium levels, lipid peroxidation, and acute bronchiolitis in infancy.

Thirty-four infants with acute bronchiolitis and 25 age-matched healthy controls were enrolled to investigate the possible relationship between serum malondialdehyde (MDA) and selenium (Se) levels and the occurrence and severity of acute bronchiolitis in children. Serum samples were taken for serum Se and MDA measurements, and the clinical score was assessed at admission. Blood was taken again from the children with bronchiolitis at 2 mo after discharge from the hospital. Mean serum MDA levels were significantly higher in patients with acute bronchiolitis than at the postbronchiolitis stage and the controls (4.2+/-2.5 nmol/L, 1.4+/-0.8 nmol/L, and 0.7+/-0.2 nmol/L, respectively [p<0.001]). Infants with bronchiolitis had lower mean serum Se levels at the acute stage than after 2 mo (31.7+/-28.9 micro g/L versus 68.4+/-26.4 micro g/L, p<0.05, respectively); both of which were significantly lower than the control group measurements (145.0+/-21.9 micro g/L) (p<0.001). There was a negative correlation between serum MDA and Se levels in the patient group (r= -0.85, p<0.001). The age of the patient, child's immunization status, parental smoking habit, and family crowding index were not correlated with serum Se, MDA levels, or clinical score at admission. In conclusion, increased MDA levels and impaired Se status demonstrate the presence of possible relationship of these parameters with pathogenesis of acute bronchiolitis, and antioxidant supplementation with Se might be thought to supply a beneficial effect against bronchiolitis.

The relationship between plasma levels of leptin and androgen in healthy and preeclamptic pregnant women.

BACKGROUND: To clarify the role of leptin and androgens in the pathogenesis of preeclampsia, we wanted to assess role of maternal leptin in women with severe and mild preeclampsia and the effects of sex steroid hormones on leptin production. METHODS: The groups consisted of 40 healthy pregnant women (HPW) as well as 55 pregnant women with severe preeclampsia (SPE) and 41 pregnant women with mild preeclampsia (MPE). No significant differences were observed between the three groups regarding age, gestational age and body mass index (BMI). Plasma leptin, total testosterone (T), estradiol (E(2)), dehydroepiandrosterone sulfate (DHEAS) and androstenedione (A) levels were measured. Statistical analysis was achieved with one-way analysis of variance (anova) followed by post hoc multiple comparisons with the Tukey honestly significant difference (HSD) test by using SPSS for Windows statistical computer program, and the Pearson's coefficient of correlation was calculated. RESULTS: The plasma level of leptin was significantly increased in the SPE and MPE groups (p < 0.001), whereas the plasma level of T was significantly increased only in the SPE group (p < 0.001). However, there was no significant difference in plasma levels of DHEAS among the three groups (p < 0.05). The plasma level of A was significantly decreased in the MPE group (p < 0.05). There was no significant difference in the plasma level of E(2) in the MPE and SPE groups (p < 0.05). There was a significant positive correlation between the plasma levels of leptin and E(2) in the MPE group (r = 0.41, p < 0.001). CONCLUSION: We concluded that the elevated plasma levels of leptin and testosterone could contribute to the endothelial dysfunction involved in the pathogenesis of preeclampsia, and that estradiol might lead to an increase in the plasma levels of leptin.

Anti-oxidant status in relation to lipoproteins, leptin and pro-inflammatory cytokines in children with steroid-sensitive nephrotic syndrome.

BACKGROUND: Reactive oxygen species and cytokines are reported to play a role in the proteinuria of nephrotic syndrome. The aim of this study was to investigate indirect evidence of oxidant activity together with leptin, lipoproteins and pro-inflammatory cytokines in children with steroid-sensitive nephrotic syndrome. METHODS: A total of 40 children with steroid-sensitive nephrotic syndrome (20 with newly onset or relapse comprised group I and 20 in remission while receiving steroids comprised group II) and 20 sex and age matched healthy control children were included. The following indirect parameters of oxidant activity were determined: serum malondialdehyde, erythrocyte superoxide dismutase, catalase and whole-blood-reduced glutathione. Serum leptin, lipids and lipoproteins were also determined. RESULTS: Similar glutathione, increased malondialdehyde levels and decreased superoxide dismutase and catalase activity were observed in group I patients compared with controls. There was no significant difference in these variables between group I and group II (P >0.05). Tumour necrosis factor-alpha and interleukin-6 concentrations were similar in patients and controls. Concentrations of interleukin-1beta and interleukin-8 were higher in the active phase of nephrotics compared with controls (P <0.05). Significant positive correlations were found between malondialdehyde and interleukin-1beta, interleukin-6, leptin and lipoprotein (a) (P <0.05). There were significant negative correlations between anti-oxidants and leptin, lipoprotein (a) and several cytokines (P <0.05). CONCLUSIONS: Changes in the concentrations of malondialdehyde, superoxide dismutase, catalase and glutathione are compatible with increased amounts of oxidation in steroid-sensitive nephrotic syndrome. Leptin and pro-inflammatory cytokines may be related to excessive protein permeability in nephrotic syndrome.