Gonul Sahin

Circulating biomarkers of oxidative stress in complicated pregnancies.

Abstract. Increased lipid peroxidation (LPO) and reduced antioxidant activity may contribute to the development of complications in pregnancy. The present study discusses the possibility of LPO and antioxidant activity in both maternal and umbilical cord blood as an indicator of oxygen radical activity. For this aim, pregnancies with hypertension and pre-eclampsia, diabetes mellitus (insulin dependent diabetes mellitus and gestational diabetes mellitus), oligohydramnios and abruptio placentae, as well as a healthy control group, were subjected in the present study. Simultaneous determination of glutathione S-transferase (GST), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT) activities and thiobarbituric acid reactive-substances (TBARs) levels were carried out in maternal erythrocyte and plasma in the antenatal period (in the third trimester) and immediately after the delivery. The same oxidative stress-related parameters were determined in umbilical cord blood as well. Erythrocyte GST activity was significantly increased in insulin-dependent diabetic pregnancy (IDDP) when compared to the control (P<0.05). Erythrocyte Se-GPx activity was found to be significantly increased in hypertensive preeclamptic pregnancy (HPP) (P<0.05) and in IDDP (P<0.05). Alterations in enzyme activities were accompanied by a simultaneous significant increase in the levels of TBARs in plasma samples of HPP (P<0.05), and IDDP (P<0.05). Enzyme activities were found to be significantly lower in cord blood samples than the maternal values, except GST. This enzyme represents about two- to threefold higher activity than those of the maternal activity in uncomplicated and complicated groups. Cord blood erythrocyte and plasma Se-GPx and CAT activities were decreased significantly in the HPP group when compared to the maternal value (P<0.05). Cord blood erythrocyte CAT activity was significantly decreased in the HPP group compared to the control (P<0.05). Cord blood TBARs levels were significantly lower than the before deliveries maternal value in the HPP group (P<0.05). No difference was detected between umbilical cord blood and maternal blood TBARs levels after delivery. The results of the present study suggest that oxidative stress and subsequent lipid peroxidation accompany the complications of hypertension, preeclampsia and diabetes mellitus in pregnancy. Maternal erythrocyte GST activity seems to be a sensitive indicator of oxidative stress in IDDP before delivery. The same enzyme can be used in cord blood as a biomarker of oxidative stress upon a sudden increase in oxygenation during delivery. These multiparameter biomarkers can also be used in monitoring the efficiency of antioxidant supplementation in complicated pregnant women, as has recently been suggested for diabetic and preeclamptic pregnancies.

Determination of aluminum levels in the kidney, liver, and brain of mice treated with aluminum hydroxide

In the present study, aluminum (Al) accumulation has been examined after aluminum loading in mice. The kidney, liver, and brain aluminum levels for mice that had been treated orally with aluminum hydroxide for 105 d and for the control group were determined using graphite furnace atomic absorption spectrophotometry (GFAAS) following an acid digestion. Matrix modifier consisted of 2% Triton X-100 and 2% Mg (NO3)2.Al loaded mice showed a significant increase in tissue aluminum levels, relative to the control group.

N-acetylcysteine, a thiol antioxidant, decreases alveolar bone loss in experimental periodontitis in rats.

BACKGROUND The purpose of this study was to analyze the morphometric and histopathologic changes associated with experimental periodontitis in rats in response to systemic administration of N-acetylcysteine (NAC). METHODS Forty-three Wistar rats were divided into five experimental groups: non-ligated (NL) group (n = 10), ligature only (LO) group (n = 10), and groups that were administered NAC systemically (7, 35, or 70 mg/kg body weight per day [NAC7, NAC35, and NAC70 groups, respectively]; n = 8, 9, and 6). Silk ligatures were placed at the gingival margin of the lower first molars in a mandibular quadrant. The study duration was 11 days, and the animals were sacrificed at the end of this period. Changes in alveolar bone levels were measured clinically and tissues were histopathologically examined to assess the differences among the study groups. RESULTS At the end of 11 days, the alveolar bone loss was significantly higher in the LO group compared to NL, NAC7, NAC35, and NAC70 groups (P <0.05). There was no statistically significant difference in the osteoclast numbers among the study groups (P >0.05), whereas the effect of NAC was dose-dependent. CONCLUSION NAC prevented alveolar bone loss in the rat model, in a dose-dependent manner, when administered systemically.

Accumulation of aluminum in rat brain: Does it lead to behavioral and electrophysiological changes?

The present study was undertaken to examine possible aluminum (Al) accumulation in the brain of rats and to investigate whether subchronic exposure to the metal leads to behavioral and neurophysiological changes in both treated and control groups. Each of the groups consisted of 10 animals. Aluminum chloride (AlCl3) at a low (50 mg/kg/d) or high (200 mg/kg/d) dose was applied to male Wistar rats by gavage for 8 wk. Al-free water by gavage was given to the control group throughout the experiment. Behavioral effects were evaluated by open-field (OF) motor activity and by acoustic startle response (ASR). Electrophysiological examination was done by recording spontaneous activity and sensory-evoked potentials from the visual, somatosensory, as well as auditory cortex. The Al content of each whole brain was determined by electrothermal atomic absorption spectrophotometry. Subchronic Al exposure slightly caused some changes in the evoked potentials and electrocorticograms and in the OF and ASR performance, but these results were not statistically significant. The brain Al levels of the control and the low and high dose of Al-exposed groups were measured as 0.717±0.208 µg/g (wet weight), 0.963±0.491 µg/g (wet weight) and 1.816±1.157 µg/g (wet weight), respectively.

Immunomodulatory effects of Turkish propolis: changes in neopterin release and tryptophan degradation.

In most of the diseases which are considered to benefit from propolis, cellular immune reaction is activated, neopterin levels in body fluids are increased and enhanced tryptophan degradation is observed. In this study, the immunomodulatory effects of six Turkish propolis samples were evaluated by using the in vitro model of peripheral blood mononuclear cells (PBMC). Concentrations of neopterin, tryptophan, kynurenine and pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were determined and also the viability of the cells was checked with trypan blue and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. In PBMC treated with mitogen phytohaemagglutinin, neopterin production and tryptophan degradation by enzyme indoleamine 2,3-dioxygenase (IDO) as well as release of cytokines was significantly enhanced and upon treatment with propolis extracts all these effects were dose-dependently suppressed. Results show an immunomodulatory effect of propolis extracts which includes down-regulation of IDO activity. IDO enzyme is considered to play an important role in the development of immunodeficiency and neuropsychiatric symptoms in patient with chronic inflammation. The suppression of tryptophan degradation by propolis extracts may therefore be related with some of its beneficial health properties in humans.

Use of 19F-nuclear magnetic resonance and gas chromatography-electron capture detection in the quantitative analysis of fluorine-containing metabolites in urine of sevoflurane-anaesthetized patients

1. The use of fluorine-19 nuclear magnetic resonance (19F-NMR) and gas chromatography-electron capture detection (GC-ECD) in the analysis of fluorine-containing products in the urine of sevoflurane-exposed patients was explored. 2. Ten patients were anaesthetized by sevoflurane for 135–660 min at a flow rate of 6 l min−1. Urine samples were collected before, directly after and 24 h after discontinuation of anaesthesia. 3. 19F-NMR analysis of the urines showed the presence of several fluorine-containing metabolites. The main oxidative metabolite, hexafluoroisopropanol (HFIP)-glucuronide, showed two strong quartet signals in the 19F-NMR spectrum. HFIP concentrations after β-glucuronidase treatment were quantified by 19F-nuclear magnetic resonance. Concentrations directly after and 24 h after discontinuation of anaesthesia were 131 ± 41 (mean ± SEM) and 61 ± 19 mol mg−1 creatinine, respectively. Urinary HFIP excretions correlated with sevoflurane exposure. 4. Longer scanning times enabled the measurement of signals from two compound A-derived metabolites, i.e. compound A mercapturic acid I (CAMA-I) and compound A mercapturic acid II (CAMA-II), as well as products from β-lyase activation of the respective cysteine conjugates of compound A. The signals of the mercapturic acids, 3,3,3-trifluoro-2-(fluoromethoxy)-propanoic acid and 3,3,3-trifluorolactic acid were visible after combining and concentrating the patient urines. CAMA-I and -II excretions in patients were completed after 24 h. 5. Since 19F-nuclear magnetic resonance is not sensitive enough, urinary mercapturic acids concentrations were quantified by gas chromatography-electron capture detection. CAMA-I and -II urinary concentrations were 2.3 ± 0.7 and 1.4 ± 0.4 mol mg−1 creatinine, respectively. Urinary excretion of CAMA-I showed a correlation with sevoflurane exposure, whereas CAMA-II did not. 6. The results show that 19F-nuclear magnetic resonance is a very selective and convenient technique to detect and quantify HFIP in non-concentrated human urine. 19F-nuclear magnetic resonance can also be used to monitor the oxidative biotransformation of sevoflurane in anaesthetized patients. Compound A-derived mercapturic acids and 3,3,3-trifluoro-2-(fluoromethoxy)-propanoic acid and 3,3,3-trifluorolactic acid, however, require more sensitive techniques such as gas chromatography-electron capture detection and/or gas chromatography-mass spectrometry for quantification.

Effects of the metals on dihydropteridine reductase activity

Metals are the oldest toxins known to human. Particularly, occupational and environmental exposure to aluminium, lead, mercury, cadmium, and manganese cause serious health problems by interaction with biological systems. Cellular targets of these metals are mostly specific biochemical processes (enzymes) and/or membranes of cells and organelles. To prevent and/or reduce the untoward or irreversible toxic effects of the metals by using biomarkers are as important as to know and to understand of their toxicity mechanisms. Dihydropteridine reductase (DHPR), which possessed essential thiol groups at the activity site, plays a crucial role in the maintenance of tetrahydrobiopterin (BH4). BH4 is the cofactor in the synthesis and regulation of neurotransmitters. A limited number of the evidences have shown that DHPR may be a target for the metals. Therefore, the present study was designed to assess possible in vitro effects of the commonly exposed metals on the enzyme activity. It was found that aluminium, cadmium, mercury, di-phenyl mercury, lead, diethyl lead, in chloride forms, and manganese, in sulphate form, led to statistically significant decreases in DHPR activity, in a concentration-dependent manner, in vitro.

Impairment of motor coordination in mice after ingestion of aluminum chloride

The mechanisms of aluminum (Al) neurotoxicity is of increasing interest. Al compounds are known to produce neurological and behavioral abnormalities in some mammalian species. The present study was designed to determine the effects of Al chloride on the skilled motor performance in mice on the rota-rod treadmill. Al chloride, depending on the duration of treatment, produced an impairment of the motor coordination ability in mice.

ALUMINUM CONTENT OF INFANT FORMULAS USED IN TURKEY

In the past few years, there has been an upsurge of interest in aluminum (Al) and human health. The well-recognized manifestations of systemic Al toxicity include fracturing osteomalacia, dialysis encephalopathy, and microcytic hypochromic anemia. The role of Al in causing childhood diseases is also becoming clearer, but the safe plasma level still remains to be determined in newborns, especially in premature newborns, implying that it should be kept low. Premature infants receiving iv fluid therapy show evidence of Al loading. Additionally, the infant-feeding mixtures, especially the soy-based infant formulas, tested may be a significant additional source of Al in the diet of infants with low birthweights, and in infants and in young children with impaired renal function. Careful clinical and biochemical monitoring is warranted to determine whether it will be necessary to eliminate Al contamination of both oral and parenteral preparations used in infants and children who may be at risk for Al intoxication. In this present study, the Al content of infant feeds was measured by electrothermal atomic absorption spectrophotometry, and also compared with those of breast milk, cow’s milk, milk powder, and some starches that are commonly used for preparation of infant feed in Turkey. Our results show that Al content of commercially available powdered infant formulas, most of which are imported from Europe, ranged from 1.211 to 10.925 μg/g. The mean value was higher than that of breast milk. It was also found that the Al content of cow’s milk in various containers was higher than that of breast milk. The highest Al level among cow’s milk samples was in the aluminized carton box.In the other products tested, such as milk powder, the starches contained Al at various levels. Among these, milk powder and rice flour contained a high level of Al.

Evaluation of Changes in Immune System of Operating Room Personnel by Measurement of Urinary Neopterin Concentrations

Abstract Today it is known that neopterin is mainly produced by activated macrophages and a marker of immune activation and macrophage activity. Increased neopterin concentrations are observed in diseases related to cellular immunity including occupational pathologies. The major goal of the present study was to evaluate the possible alteration of neopterin levels in operating room personnel, and also to show whether screening of neopterin may be useful to monitor the effect of occupational anesthetic exposure on the cellular immune system. Therefore, urinary neopterin to creatinine levels in both, exposed workers (n = 40) and healthy volunteers (n = 30), were measured by using high-performance liquid chromatography. At the same time, the correlation among urinary neopterin levels and working years, age, and smoking status were evaluated. Compared to controls, urinary neopterin levels in the exposed group were increased (controls: 85 ± 16 μmol/mol creatinine, workers: 151 ± 39 μmol/mol creatinine; p <0.05). The findings suggest that the follow up of neopterin levels may have diagnostic value in possible occupational exposure-related immune system disorders. Moreover, its biological monitoring should be performed in workplaces for clinical diagnosis and prognosis.