The nephroprotective effect of amifostine in a cecal ligation-induced sepsis model in terms of oxidative stress and inflammation.

OBJECTIVE: Sepsis is responsible for more than 5 million deaths worldwide every year. The purpose of this study was to use amifostine to reduce acute kidney injury developing as a result of sepsis. MATERIALS AND METHODS: Thirty Sprague Dawley rats were divided into three equal groups - a healthy control group (Group 1), cecal ligation and puncture group (CLP, Group 2), and a CLP + amifostine (AMF) group receiving a total of 200 mg/kg AMF intraperitoneally (i.p.) 15 min before sepsis induction (Group 3). RESULTS: Total thiol levels decreased while malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB/p65), and interleukin (IL)-1ß, and IL-6 levels increased in the CLP group. We also observed degeneration in renal corpuscles, necrotic tubules, polymorphonuclear leukocyte inflammation, and vascular congestion. In the amifostine group, total thiol levels in tissue increased, while MDA, TNF-α, NF-кB/p65, IL-1ß, and IL-6 levels, necrotic renal tubules, and inflammation decreased. CONCLUSIONS: Amifostine prevented sepsis-related acute kidney injury by reducing inflammation and oxidative stress.

The effect of imatinib administered in the prenatal period on testis development in rats.

BACKGROUND: The purpose of this study was to examine the effects of exposure to imatinib in the prenatal period on testis development in rats. METHODS: Although all the study groups received intraperitoneal imatinib on prenatal days 1-8, no pregnancy occurred in the Imatinib-80 group. Immunohistochemical analysis, TUNEL, c-kit and PDGF staining revealed no difference between the groups in terms of positivity scoring. RESULTS: A significant decrease was detected in total sperm counts in the Imatinib-20 group compared to the control group, but the sperm count was higher in the Imatinib-60 group than in the Imatinib-20 group. At biochemical measurements, the drug increased oxidative stress in the testis and serum in the Imatinib-20 group, but caused a decrease in tissue in the Imatinib-60 group. Thiol measurements revealed a decrease in the testis and serum in the Imatinib-60 group, while an increase in serum measurements was observed in the Imatinib-40 group. Analysis revealed no difference between the groups in terms of protamine and histone gene expression levels in testis tissue exposed to imatinib. CONCLUSION: Our findings show that prenatal exposure to imatinib can lead to histopathological and biochemical changes in testis tissue, but that no adverse effect occurs in nuclear maturation of germ cells during spermiogenesis.

Lasting hepatotoxic effects of prenatal mobile phone exposure.

OBJECTIVE: In this study, the livers of rats born to mothers exposed to electromagnetic field (EMF) were examined 60 days postpartum for biochemical and histopathological changes. METHODS: Pregnant rats were exposed to radiation (900 MHz EMF, 24 h/day for 20 days) using a digital signal generator by placing the device centrally under the cage, which formed the study (EMF) group, while untreated matching rats served as controls. Livers and blood were obtained from litters (seven males and seven females) of both groups 60 days after birth, which were used for biochemical and histopathological analyses. RESULTS: There was a significant increase in the levels of malondialdehyde (MDA) (p < 0.05) that was accompanied by a significant fall in glutathione (GSH) (p < 0.01) in the liver. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly increased (p < 0.05). Histopathologically, the liver sections of the EMF group showed intense degeneration in hepatocytes with cytoplasmic eosinophilic structures, pyknotic nuclei and fibrosis. CONCLUSION: We demonstrate that the intrauterin harmful effects of EMF on the livers of rats persist into adulthood.

Comparision of inflammatory biomarkers for detection of coronary stenosis in patients with stable coronary artery disease.

BACKGROUND: The objective of the current study was to evaluate the role of various inflammatory biomarkers in detection of coronary stenosis in patients with stable coronary artery disease (CAD) and healthy people. METHODS: A total of 111 patients with stable coronary artery disease, and 66 healthy subjects were enrolled in the study. Serum levels of lipoprotein-associated-phospholipase A2 (Lp-PLA2), high-sensitivity C-reactive protein (hs-CRP), and myeloperoxidase (MPO) were measured to compare patient and control groups. RESULTS: Baseline characteristics were similar between healthy and patient groups, with the exception of age. ANCOVA and log-transformed data of inflammatory biomarkers revealed that, Lp-PLA2 (p < 0.001) and hs-CRP (p < 0.05) levels in all patient groups were significantly higher than in the control group. Conversely, there was no significant difference in MPO levels among groups. CONCLUSIONS: In stable CAD patients, serum Lp-PLA2 levels are more compatible than hs-CRP and MPO levels in the detection of coronary stenosis.      

Decreased nitric oxide end-products and its relationship with high density lipoprotein and oxidative stress in people with type 2 diabetes without complications.

Diabetes mellitus is associated with hyperglycaemia, hyperlipoproteinaemia, increased oxidative stress and decreased nitric oxide production from endothelial cells. In the present study the aim was to determine the relationships between serum lipids, lipoproteins, erythrocyte malondialdehyde (eMDA), as a marker for oxidative stress, and serum nitrite and nitrate levels, as degradation products of nitric oxide in type 2 diabetic patients without complications. The study group included 30 patients and 30 sex- and age-matched healthy volunteers. Total cholesterol, triacylglycerol, LDL cholesterol, apo B, HbA(1c) and glucose levels in patients were significantly higher than in controls, and HDL cholesterol levels lower. Increased eMDA levels and decreased nitrate and nitrite+nitrate levels (+/-SD) were observed in patients compared to controls (87+/-22 vs 59+/-17 nmol/g-Hb (P<0.01); 11.8+/-8.6 vs 22.8+/-10.8 micromol/l (P<0.01); and 16.8+/-11.0 vs 28.8+/-11.3 micromol/l (P<0.01), respectively). When the patients were divided into two groups according to HDL cholesterol levels (< or =0.91 and >0.91 mmol/l), total plasma nitric oxide end-products were found to be decreased in patients with low HDL levels compared to those patients with high HDL levels [men, 11.7+/-6.4 vs 24.6+/-14.9 micromol/l (P<0.01); women, 12.5+/-6.6 vs 21.4+/-6.6 micromol/l (P<0.01]. Nitrite and nitrate levels were correlated with HDL cholesterol (r=0.50, P<0.05) and eMDA (r=-0.52, P<0.05). It was concluded that the patients with unregulated blood glucose levels have abnormal lipid and lipoprotein metabolism and decreased nitric oxide end-products, with relationships between nitric oxide products and dyslipidaemia, especially between low HDL cholesterol levels and increased oxidative stress.

The effect of ATP-MgCl(2) on prevention of reperfusion injury after unilateral testicular torsion.

This study was designed to investigate the effect of ATP-MgCl(2) administered before and after detorsion on the prevention of reperfusion injury after unilateral testicular torsion. The rats were divided into six groups, each containing six rats. Torsion was created by rotating the left testes 720 degrees in a clockwise direction. Group 1 functioned as a control group. Torsion only was carried out in Group 2. Detorsion was carried out in Group 3. ATP-MgCl(2) (100 micromol/kg) was injected intravenously immediately before detorsion in Group 4. ATP-MgCl(2) (100 micromol/kg) was injected intravenously immediately after detorsion in Group 5. Saline was injected intravenously immediately after detorsion in Group 6. The effect of ATP-MgCl(2) on reperfusion injury was investigated by determining the levels of thiobarbituric acid-reactive substances (TBAR) and resulting lipid peroxidation in the bilateral testicular tissue. Testicular torsion and detorsion caused a significant increase in the TBAR levels in the bilateral testicular tissue. TBAR levels decreased to approximately normal levels in Groups 4 and 5. It is concluded that if reperfusion injury has occurred in both testes after unilateral testicular torsion, ATP-MgCl(2) administered before or after detorsion may prevent reperfusion injury in testicular torsion.

Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments.

BACKGROUND: Reactive oxygen species (ROS) may play a role in some neuropsychiatric disorders. There is some evidence that the activation of immune-inflammatory process, increase of monoamines catabolism, and abnormalities in lipid compounds may cause overproduction of ROS and, in turn, antioxidative enzyme activities (AEAs) and lipid peroxidation (LP), and that these phenomena may be related to pathophysiology of major depression. METHODS: The aims of this study were (i) to examine the AEAs and LP levels of the major depressed (MD) patients, and to compare these with healthy controls; and (ii) to investigate the effect of subchronic treatment with selective serotonin reuptake inhibitors (SSRIs) on AEAs and LP levels in MD subjects. Thirty MD patients, and 32 healthy controls (HC) participated in this study. AEAs and LP levels were determined by measuring several antioxidative enzymes and malondialdehyde (MDA) levels in plasma and/or in red blood cells. RESULTS: Major depressed patients, especially melancholic patients, had higher AEA and LP levels than those of healthy controls. After treatment for 3 months with SSRIs, AEA and LP levels of the patients were significantly decreased to normal levels. CONCLUSION: These findings suggest that (i) major depression, especially with melancholia, is associated with elevated AEAs and LP, and that (ii) subchronic treatment with SSRIs may have a suppressive effect on AEA and LP. CLINICAL IMPLICATION AND LIMITATION: AEAs might be used for monitoring SSRIs effects.

Oxidative damage of erythrocyte membrane in nephrotic syndrome.

Erythrocytes are target cells for peroxidative damage. Abnormal susceptibility of erythrocyte lipids to peroxidation is believed to reflect a similar abnormality in other organs and tissues. The changes in erythrocyte lipid peroxidation [measured by malonyldialdehyde (MDA) concentration] and erythrocyte membrane cholesterol (EMC) and their correlation with plasma lipid changes were studied in 36 children with steroid-responsive minimal change nephrotic syndrome (MCNS) (16 in relapse, 20 in remission) and 30 matched healthy controls. Erythrocyte MDA levels were significantly higher in relapse [126.3+/-40.6 nmol/g hemoglobin (Hb)] compared with remission (101.2+/-21.3 nmol/g Hb, P<0.02) and in controls (95.4+/-20.4 nmol/g Hb, P<0.001). Plasma MDA levels in relapse were also higher than in remission (4.26+/-1.19 nmol/ml vs. 3.16+/-1.18 nmol/ml, P<0.01), and in controls (2.49+/-0.86 nmol/ml, P<0.001). The EMC content changed significantly during remission (1.22+/-0.15 mg/10(10) cells in relapse, 1.09+/-0.19 mg/10(10) cells in remission, P<0.04). These results show an increased sensitivity of red cells to lipid peroxidation in patients with steroid-sensitive nephrotic syndrome without the development of renal failure and anemia. Lipid peroxidation of plasma lipids and erythrocyte membrane may be a primary phenomenon, but this should be confirmed by investigation of peroxidation of renal lipids.

Relationship between lipid peroxidation and disease activity in patients with Behçet's disease.

Behçet's disease is a chronic multi-systemic disorder which is characterized by a relapsing systemic inflammatory process. The alteration of lipid profile and lipid peroxidation resulting from the inflammatory process may he associated with an increased risk for atherosclerosis in patients with Behcet's disease. We investigated lipids, lipoprotein and lipid peroxidation and their inter-relationships considering the disease activity. Eighteen patients (11 male and 7 female) and 20 age-matched healthy subjects (10 male and 10 female) were studied. Lipid profile including total cholesterol, triacylglycerol, HDL-cholesterol, LDL-cholesterol, lipoprotein(a), apoAI and apoB, and acute phase reactants including polymorphonuclear (PMN) elastase, PMN leukocyte count, erythrocyte sedimentation rate (ESR) and complements (C3, C4) were evaluated in patients in active and inactive periods of Behçet's disease and control subjects. The levels of thiobarbituric acid reactive substance (TBARS) were assessed as an indicator of lipid peroxidation. Lipid peroxidation was found to he increased in the active period compared to the inactive period of the disease and control subjects. Also, lipid peroxidation showed correlations of various degrees with atherogenic lipid parameters in both periods of the followed-up patients. In conclusion, patients with Behçet's disease in the active period may be much more susceptible to atherogenic events than those in the inactive period of the disease and control subjects.