Oxidative stress parameters and inflammatory and immune mediators as markers of the severity of sepsis.

INTRODUCTION: Sepsis is a complex inflammatory syndrome with diverse etiology and wide spectrum of severity. The aim of this study was to investigate whether inflammatory mediators, in comparison with oxidative parameters, are associated with severity of sepsis. METHODOLOGY: Plasma neopterin, adenosine deaminase (ADA), vascular cell adhesion molecule (VCAM), intracellular adhesion molecule (ICAM), interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNF-α), as inflammatory mediators, and serum nitric oxide (NOx), nitrotyrosine (NT), oxidized LDL (oxLDL) levels, serum paraoxonase 1 (PON1) activity, and erythrocyte glutathione (GSH) levels as oxidative stress parameters of 12 patients with mild sepsis, 25 patients with severe sepsis, and 20 healthy control subjects were evaluated. NOx, GSH levels and PON1 activity were determined by colorimetric methods, whereas neopterin, VCAM, ICAM, IL-1, IL-6, TNF-α, NT, and oxLDL levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: All parameters in mild and severe sepsis were significantly different from those of healthy subjects, except ADA activities. Patients with severe sepsis exhibited higher IL-6, TNF-α, NT, and oxLDL levels than patients with mild sepsis. GSH (98%, 98%), oxLDL (98%, 98%), VCAM-1 (99%, 99%), and ICAM-1 (99%, 99%) have much more sensitivitiy and specificity in sepsis. CONCLUSIONS: Our results suggest that the oxidative stress and inflammatory response in patients with sepsis were increased and that serum IL-6, TNF-α, NT, and oxLDL levels were correlated with the severity of sepsis. Therefore, increases in these parameters may contribute to the dysfunction or failure of one or more organs, or even death, in sepsis.

The effect of chronic long-term intermittent hypobaric hypoxia on bone mineral density in rats: role of nitric oxide.

Intermittent hypoxia is the most common pattern of hypoxic exposure in humans. The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on bone metabolism is not investigated. We examined the effect of CLTIHH on bone metabolism and the role of nitric oxide (NO) in this process. The rats were divided into three groups in this study. The animals in groups I and II have been exposed to CLTIHH. The animals in group II were also treated with nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. To obtain CLTIHH, rats were placed in a hypobaric chamber (430 mm Hg; 5 h/day, 5 days/week, 5 weeks). The group III (control) rats breathed room air in the same environment. At the begining of the experiments, bone mineral density (BMD) of the animals were measured, and blood samples were collected from the tail vein. After the 5-week CLTIHH period, the same measurements were repeated. Parathyroid hormone, calcium, phosphate, bone alkaline phosphatase (b-ALP), NO, interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha levels were determined. The cytokines, NO levels, and BMD in CLTIHH-induced rats were higher compared with baseline and control values. The cytokines, b-ALP, and BMD increased while NO levels decreased in the group II compared with baseline values. BMD values of group II were lower than group I but higher than control group. Our results suggested that CLTIHH has positive effects on bone density. Intermittent hypoxia protocols may be developed for treatment and prevention of osteopenia and osteoporosis.

The clinical and biochemical presentation of vitamin D deficiency and insufficiency in children and adolescents.

AIM: To evaluate the clinical and biochemical findings of the children and adolescents with vitamin D deficiency and insufficiency in order to determine the clinical and biochemical presentation differences between age groups. METHODS: This retrospective study included a review of medical reports of 543 patients (aged between 1-17 years) who were referred to our hospital between October 2011 and May 2012 with symptoms related to vitamin D deficiency or insufficiency. The patients were divided into four groups by age: 1-3 years (Group 1), 4-6 years (Group 2), 7-11 years (Group 3) and 12-17 years (Group 4). Patients diagnosed with vitamin D deficiency or insufficiency were evaluated as to their clinical and biochemical findings. RESULTS: Gender distribution were not statistically different between the four groups. The mean ages of Groups 1-4 were 1.9±0.7, 5.1±0.9, 8.9±1.3, 13.1±1.1, respectively. Major complaints on admission were muscle weakness (91%), low weight gain (failure to thrive) (89%), head deformity (frontal bossing) (35.6%), bone deformity (enlargement of wrist and ankles) (29.7%) for Group 1. Muscle weakness (76%) and low weight gain (failure to thrive) (68%) for Group 2. Leg and chest pain were the major symptoms in Group 3 (57% and 28%, respectively) and in Group 4 (26% and 55%, respectively) as well as high rates of obesity (31% and 63%). The biochemical findings of vitamin D deficiency mostly appeared in the first group who developed vitamin D deficiency due to the lack of vitamin D supplementation. However, in older children, the majority of the patients had low 25 hydroxyvitamin D (25 OHD) values without evidence of biochemical findings of osteomalacia. CONCLUSION: Depending on the degree of deficiency and insufficiency, and the age of the patients, the clinical and biochemical findings varied widely. Children under the age of 3 who either never received vitamin D supplementation or who had been receiving supplementation that was stopped too early were at a greater risk for developing clinically and biochemically proved vitamin D deficiency. In older children, low vitamin D levels mostly resulted in subtle complaints without abnormal biochemical findings.

Darbepoetin α ameliorates neuronal damage in a rat model of acute ethanol intoxication.

OBJECTIVE: Acute ethanol intoxication has been shown to cause oxidative damage in many organ systems including the brain. Erythropoietin has antioxidant effects and prevents neuronal damage in the animal model of ischemic brain injury. In this study, we aimed to investigate the effects of darbepoetin alpha, an analog of erythropoietin with a longer half-life and higher in vivo activity, on ethanol-induced acute brain injury. METHODS: Forty-eight Wistar albino rats were allocated to four groups. The first group received ethanol treatment (E), the second group was treated with ethanol and darbepoetin (ED), the third group received only saline treatment (S), and the fourth group received both saline and darbepoetin treatment (SD). Plasma S100-ß and neuron-specific enolase (NSE) levels were measured. Histopathological evaluation of the brains was performed. RESULTS: The plasma S100-ß and NSE levels were significantly lower in group ED compared with group E. In group E, we have observed focal red-neuron formation at the granular layer of the dentate gyrus. We did not observe any histopathological changes in the other groups (ED, S, and SD). CONCLUSION: Our findings suggest that darbepoetin alpha has neuroprotective effect in acute ethanol intoxication, possibly through its antioxidant effect.

Protein oxidation markers in women with and without gestational diabetes mellitus: a possible relation with paraoxonase activity.

AIMS: To clarify the levels of protein oxidation markers such as protein carbonyl (PCO), protein hydroperoxides (P-OOH), advanced oxidation protein products (AOPP) and nitrotyrosine (NT), as well as antioxidative enzymes such as paraoxonase (PON-1) in women with and without gestational diabetes mellitus (GDM). METHODS: The study was conducted on 23 women with GDM and 22 women without GDM. The levels of the P-OOH, AOPP, and PON-1 were determined by colorimetric methods; whereas NT and PCO levels were measured by ELISA. RESULTS: The concentrations of protein oxidation markers were significantly increased and PON1 activity was significantly decreased in GDM group compared to those of normal pregnant women. The control group showed a significant negative correlation between PON-1 and PCO (r=-0.451, p=0.027); whereas in GDM group, there was a significant positive correlation between P-OOH and HbA1c (r=0.89, p=0.001). There was no significant correlation between AOPP, PON-1, P-OOH, PCO, and HbA1c in either group. CONCLUSIONS: There is evidence of a possible association between protein oxidation and decreased PON1 activity in GDM. The increase in protein oxidation parameters in the GDM group leading to decreased PON1 activity might, we think, create a predisposition for clinical complications in GDM group.

Effects of lycopene on oxidative stress and remnant liver histology after partial hepatectomy in rats.

BACKGROUND/AIMS: Partial hepatectomy is performed for the treatment of mass lesions in the liver. Lycopene, which is a carotenoid, is present in various physiologic processes. In this study, the effects of lycopene administration in partially hepatectomized rats were evaluated by assessing various oxidant/antioxidant parameters, remnant liver histology and plasma nitric oxide levels. METHODS: Thirty Wistar albino adult male rats were randomly divided into three equal groups as: Sham, Partial Hepatectomy and Lycopene-Administered + Partial Hepatectomy groups. Lycopene (4 mg/kg), which was dissolved in olive oil, was given to the rats per orally (via gavage tube) (0.1 ml) every day for 6 weeks before partial hepatectomy and for one week after partial hepatectomy. Tissue and blood samples were collected one week after partial hepatectomy. RESULTS: Plasma malondialdehyde (p<0.001) and nitric oxide (p<0.05) levels in the lycopene-administered + partial hepatectomy group were significantly higher than in the partial hepatectomy group. Intraerythrocytic glutathione (p<0.001), plasma (p<0.001) and liver tissue Cu-Zn (p<0.05) superoxide dismutase levels of the lycopene-administered + partial hepatectomy group were significantly lower than in the partial hepatectomy group. CONCLUSIONS: Lycopene administration could be harmful by increasing oxidative stress after partial hepatectomy.

Evaluation of oxidative stress markers in first trimester for assessment of preeclampsia risk.

AIM: The aim of this study is to determine the predictive values of oxidative stress markers and antioxidants in the development of preeclampsia between 10-14 and also at 20-24 weeks of gestation, after the completion of vascular transformation. MATERIALS AND METHODS: Levels of oxidative stress parameters such as malondialdehyde (MDA), lipidhydroperoxide (LHP) and prostaglandin F(2α) (PGF(2α)), oxidized LDL (oxLDL), and antioxidant status parameters such as paraoxonase 1 (PON1), superoxide dismutase (SOD) and total antioxidant capacity (TAC) levels were measured and compared in 21 preeclamptic and 24 healthy pregnant women. RESULTS: In preeclamptic women, both between 10-14 and also at 20-24 weeks of gestation the levels of oxLDL, MDA and PGF(2α) were significantly higher (P < 0.001, P < 0.001, respectively), PON1, SOD and TAC were significantly lower (P < 0.01, P < 0.001, P < 0.05, respectively) compared to healthy pregnant women; yet there was no significant difference in LHP levels. CONCLUSION: Increased levels of serum MDA and PGF(2α), low levels of SOD and PON1 activity, in 10-14 GW may have been associated with preeclampsia etiology. High levels of MDA and PGF(2α) indicate that the oxidative damage is present well before the clinical symptoms occur. A panel of oxidative stress markers such as MDA and PGF(2α) in maternal blood can predict the development of preeclampsia long before clinical onset.

Serum paraoxonase activity and oxidative DNA damage in patients with laryngeal squamous cell carcinoma.

OBJECTIVES: To determine the possible role of oxidants and antioxidants in the pathogenesis of in laryngeal squamous cell carcinoma. DESIGN AND SETTING: Our study involved patients with newly diagnosed laryngeal cancer (n = 29) and same age- and sex-matched healthy individuals (n = 21). Serum malondialdehyde (MDA) and paraoxonase (PON1) levels were measured by colorimetric methods and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) was measured using enzyme-linked immunosorbent assay in fasting blood samples of participants. RESULTS: The levels of 8-OH-dG (control, 4.61 ± 1.27 ng/mL; patient, 11.70 ± 2.44 ng/mL; P < 0.001) and MDA (control, 4.16 ± 1.02 nmol/mL; patient, 8.74 ± 1.65 nmol/mL; P < 0.001) were significantly higher, and those of PON1 (control, 170.86 ± 72.46 U/mL; patient, 80.44 ± 29.81 U/mL; P < 0.001) were significantly lower in patients. There were no statistically significant differences in the 8-OH-dG, MDA levels, and PON1 activity in relation to T (tumor) staging of differentiation and different smoking/drinking status. There was a statistically significant difference in MDA levels (10.24 ± 0.64 nmol/mL) only in stage II laryngeal cancer. There were a statistically significant positive correlation between serum MDA and 8-OH-dG (r = 0.887, P < 0.001), a statistically significant negative correlation between serum MDA and serum PON1 (r = -0.477, P < 0.01), and a statistically significant negative correlation between serum 8-OH-dG and serum PON1 in patients (r = -0.420, P < 0.05). CONCLUSIONS: We conclude that, in patients with laryngeal squamous cell carcinoma, the oxidant/antioxidant balance was impaired in favor of lipid peroxidation and DNA damage.

Ezetimibe therapy and its influence on oxidative stress and fibrinolytic activity.

OBJECTIVE: The effect of ezetimibe on blood lipids, oxidative stress, and fibrinolytic activity in hyperlipidemic patients was investigated after three months of therapy. METHODS: Thirty hyperlipidemic patients were treated for twelve weeks with ezetimibe 10 mg/day. A healthy control group with matching age and gender was also included. Fasting blood glucose, lipid parameters, paraoxonase (PON1), protein carbonyl (PCO), oxidized LDL (oxLDL), 8-isoprostane (ISOPR), total antioxidant capacity (TAC) levels, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type-1 (PAI-1), and PAI-1/t-PA levels were evaluated. RESULTS: Ezetimibe therapy for twelve weeks led to changes in lipid profile in accordance with the literature. Fibrinolytic activity parameters, PAI-1/tPA and tPA-1 decreased, whereas PAI-1 levels did not change significantly. Antioxidant parameters, serum PON1 activity, and TAC levels increased significantly compared with the basal values. Oxidant parameters, oxLDL, ISOPR, and PCO (which is an indicator of oxidative protein damage) decreased significantly after therapy. CONCLUSIONS: Ezetimibe therapy has beneficial effects on fibrinolytic activity and homeostasis between oxidant and antioxidant activity in hyperlipidemic patients This may be through lowering lipid levels or other mechanisms such as decreasing insulin resistance and the pleiotropic effects of the drug.

Raloxifene decreases serum malondialdehyde and nitric oxide levels in postmenopausal women with end-stage renal disease under chronic hemodialysis therapy.

AIM: We prospectively aimed to investigate the relationship between raloxifene administration and serum malondialdehyde (MDA), nitric oxide (NO), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride levels in postmenopausal women undergoing hemodialysis treatment for chronic renal failure. METHODS: Twenty-four women scheduled for twice-weekly hemodialysis treatment were given 60 mg/day raloxifene for 3 months. Serum MDA, estimated NO, HDL, and LDL measurements were assessed initially and at month 3. We used the Mann-Whitney U and Wilcoxon signed-rank tests for comparisons. Five women discontinued the study. RESULTS: After controlling for baseline characteristics, mean serum MDA and estimated NO levels decreased (P = 0.0001 and P = 0.0001, respectively) from 2.01 +/- 0.40 micromol/L and 21.3 +/- 17.9 micromol/L at baseline to 1.27 +/- 0.23 micromol/L and 7.7 +/- 7.5 micromol/L at month 3, respectively. Mean serum LDL level declined (P = 0.004) from 120.0 +/- 24.3 mg/dL to 103.3 +/- 12.1 mg/dL, and mean HDL level increased (P = 0.024) from 52.2 +/- 7.8 mg/dL to 57.2 +/- 5.7 mg/dL with raloxifene administration. CONCLUSION: Oral raloxifene administration (60 mg/day) for 3 months lowered serum MDA and NO levels with favorable effects on serum lipid parameters in postmenopausal women, who were undergoing long-term hemodialysis treatment for chronic renal failure.

Effect of vitamin C on oxidative liver injury due to isoniazid in rats.

BACKGROUND: The aim of the present study was to investigate the effect of different doses of vitamin C on oxidative liver injury due to isoniazid (INH) in rats. METHODS: Rats were divided into four subgroups, each containing 10 rats. Group 1 was the control group; group 2, INH 50 mg/kg per day; group 3, INH 50 mg/kg per day + low-dose vitamin C (100 mg/kg per day); group 4, INH 50 mg/kg per day + high-dose vitamin C (1000 mg/kg per day). INH and vitamin C were administered into their stomachs through an oral tube. After 21 days, measurements were made in both serum and homogenized liver tissues. The levels of glutathione (GSH), superoxide dismutase (SOD) and other biochemical variables were measured. Malondialdehyde (MDA), glutathione peroxidase (GSH-px) and vitamin C were measured using commercial kits. RESULTS: Aspartate amino transferase and alanine aminotransferase in group 2 were higher than those in groups 1, 3 and 4 (P < 0.008 for both). Serum and tissue levels of MDA in group 2 were higher than that in groups 1 and 3 (P < 0.008 for both). There was no difference in the SOD levels between the four groups (P= 0.095). Erythrocyte and tissue GSH in group 2 were higher than that in groups 1 and 3 (P < 0.008 for both). Interestingly, erythrocyte and tissue GSH in group 4 were lower than those in group 1 (P < 0.008 for both). Erythrocyte level of GSH-px in group 2 was higher than that in groups 1 and 3 (P < 0.008 for both). CONCLUSIONS: INH-induced liver injury is associated with oxidative stress, and co-administration of low-dose vitamin C may reduce this damage effectively in a rat model. The antioxidant effect of high-dose vitamin C does not seem more potent compared to the low dose.

Gender difference as regards myocardial protein oxidation in aged rats: male rats have increased oxidative protein damage.

OBJECTIVE: The reasons for the difference in life expectancy between males and females are still unknown. Previous studies have provided compelling evidence for the presence of oxidized proteins, and lipids in advanced human atherosclerotic lesions. The gender factor responsible for such protein oxidation is unknown and controversial. Our aim was to reveal the difference between myocardial protein and lipid oxidation parameters of male and female aged rats. METHODS: We investigated the relation between myocardial protein carbonyl (PCO) and other protein oxidation parameters such as advanced oxidation protein products (AOPP), nitrotyrosine (NT), protein hydroperoxide (P-OOH), and protein thiol (P-SH). Our study also covered other oxidative stress parameters, such as total thiol (T-SH), non-protein thiol (Np-SH), 4-hydroxyalkenal (4-HAE), malondialdehyde (MDA), reduced glutathione (GSH), and the glutathione disulfide (GSSG). RESULTS: Among the studied parameters, myocardial PCO, AOPP, NT, Np-SH, GSH, Fe(2+) levels and the redox index (RI) of male rats were significantly higher than in the female group. On the other hand, P-OOH, P-SH, T-SH, 4-HAE, and MDA levels were all found to be not different. CONCLUSIONS: These data support the hypothesis that elevated levels of PCO, AOPP, and NT contribute to the extent of protein, but not lipid, oxidation in aged male rats. We are of the conviction that the increased myocardial Np-SH, GSH and RI levels that we have determined in aged male rats may be a protective factor in propagation of protein oxidation. Our findings support our conviction that protein and lipid oxidation, in the myocardial tissue of aged rats, have a controlling role in differing regulating mechanisms through gender differences.

Serum paraoxonase (a high-density lipoprotein-associated lipophilic antioxidant) activity and lipid profile in experimental acute pancreatitis.

OBJECTIVE: This study was designed to determine the serum lipid profile and the activity of paraoxonase (PON1, the lipophilic antioxidant component of high-density lipoprotein [HDL]-cholesterol) in acute pancreatitis. METHODS: Acute pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. Oxidative stress marker (malonyldialdehyde), lipid profile, and PON1 activity were determined in the serum. RESULTS: In the acute pancreatitis group, whereas the mean levels of total cholesterol, low-density lipoproteins, and malonyldialdehyde were significantly higher (P < 0.001 for each), HDL level and PON1 activity were found to be significantly lower (P < 0.001 for each). CONCLUSIONS: Our results suggest that an abnormal lipid profile and decreased PON1 activity may have a role in the pathogenesis of acute pancreatitis in which HDL-associated antioxidant defense is impaired.