Ferah Armutcu

Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism.

Abstract.There is great evidence in recent years that oxygen free radicals play an important role in the pathophysiology of many neuropsychiatric disorders. The present study was performed to assess the changes in red blood cells thiobarbituric acid-reactive substances (TBARS) levels, and superoxide dismutase (SOD), catalase (CAT), adenosine deaminase (ADA) and xanthine oxidase (XO) activities in patients with autism (n = 27) compared to age- and sex-matched normal controls (n = 26). In the autistic group, increased TBARS levels (p < 0.001) and XO (p < 0.001) and SOD (p < 0.001) activity, decreased CAT (p < 0.001) activity and unchanged ADA activity were detected. It is proposed that antioxidant status may be changed in autism and this new situation may induce lipid peroxidation. These findings indicated a possible role of increased oxidative stress and altered enzymatic antioxidants, both of which may be relevant to the pathophysiology of autism.

Vitamin E against oxidative damage caused by formaldehyde in frontal cortex and hippocampus: biochemical and histological studies.

Formaldehyde (FA) can cause severe central nervous system impairment. But, there are only a few studies about biochemical and histopathological changes of frontal cortex and hippocampal tissue caused by FA toxicity. The aim of our study was to investigate these changes occurring after chronic formaldehyde toxicity in frontal cortex and hippocampal tissues, and protective effect of Vitamin E (vit E) against oxidative damage. Eighteen rats were divided into three groups: (1) control, (2) treated with FA (FAt), and (3) treated with FA and vit E (FAt+vit E) groups. After the treatment, the animals were sacrificed and frontal cortex and hippocampal tissues were removed for biochemical and histopathological investigation. FA significantly increased tissue malondialdehyde (MDA) and protein carbonyl (PC) levels and also decreased superoxide dismutase (SOD) and catalase (CAT) enzyme activities in frontal cortex and hippocampal tissue compared to control. Vit E treatment decreased MDA and PC levels and prevented inhibition of SOD and CAT enzymes in the tissues. In the FAt group, the neurons of both tissues became extensively dark and degenerated with picnotic nuclei. The morphology of neurons in FAt+vit E group was protected well, but not as neurons of the control group. The number of neurons in frontal cortex and hippocampal tissue of FAt group was significantly less than both control and FAt+vit E groups. It was concluded that vit E treatment might be beneficial in preventing FA-induced oxidative frontal cortex and hippocampal tissue damage, therefore, shows potential for clinical use.

Antiepileptogenic and antioxidant effects of Nigella sativa oil against pentylenetetrazol-induced kindling in mice

Nigella sativa oil (NSO), a herbaceous plant, has been used for thousands of years for culinary and medical purposes. This study aimed to investigate the anticonvulsant and antioxidant activities of NSO on pentylenetetrazol (PTZ) kindling seizures in mice. Nigella sativa oil was tested for its ability (i) to suppress the convulsive and lethal effects of PTZ in kindled mice (anti-epileptogenic effect), (ii) to attenuate the PTZ-induced oxidative injury in the brain tissue (antioxidant effect) when given as a pretreatment prior to each PTZ injection during kindling acquisition. Valproate, a major antiepileptic drug, was also tested for comparison. Both substances studied significantly decreased oxidative injury in the mouse brain tissue in comparison with the PTZ-kindling group. Nigella sativa oil was found to be the most effective in preventing PTZ-induced seizures relative to valproate. Nigella sativa oil showed anti-epileptogenic properties as it reduced the sensitivity of kindled mice to the convulsive and lethal effects of PTZ; valproate was ineffective in preventing development of any of these effects. The data obtained support the hypothesis that neuroprotective action of NSO may correlate with its ability to inhibit not only excessive reactive oxygen species (ROS) formation but also seizure generation.

Elevated serum nitric oxide and superoxide dismutase in euthymic bipolar patients: impact of past episodes.

Nitric oxide (NO) has been implicated to play a role in the pathogenesis of many neuropsychiatric disorders. NO level was found high in acute manic inpatients. In this study, we aimed to assess NO level and activity of the antioxidant enzyme, superoxide dismutase (SOD), in euthymic bipolar patients. Twenty-seven patients with bipolar disorder (BD) in euthymic phase, and 20 healthy volunteers were included in this study. A semi-structured form was used to note social, demographic and clinical parameters of the patients. NO level and SOD activity were studied in the serum samples obtained from the patients and controls. The mean serum NO level in BD was significantly higher than in controls. Mean serum SOD activity was found to be elevated in patients with BD compared to controls. Total number of the manic episodes correlated with NO levels, but not with SOD activity. In conclusion, the number of manic episodes is positively associated with NO levels. NO and SOD appear to have a pathophysiological role in BD, especially in Type I euthymic phase, and may be considered an available trait marker for BD.

Oxidant-antioxidant enzymes and lipid peroxidation in generalized vitiligo

Vitiligo is a common pigmentary disorder of the skin with selective destruction of melanocytes. The pathogenetic mechanisms in vitiligo have not been completely clarified. The aim of our investigation was to evaluate the oxidative stress in the pathogenesis of generalized vitiligo. Twenty‐seven patients with generalized vitiligo and 24 phototype‐, age‐, and sex‐matched healthy controls were included in this study. We analysed serum levels of malondialdehyde (MDA), nitric oxide (NO), and serum activities of superoxide dismutase (SOD) and xanthine oxidase (XO) in the patients with vitiligo and in the controls. We found significantly higher levels of MDA and XO activity (P < 0.001 and P < 0.05, respectively), and a significantly lower level of serum SOD activity (P < 0.05) in patients with vitiligo compared with the controls. However, the increase in the level of serum NO was insignificant (P > 0.05). These results suggest that lipid peroxidation of cellular membrane of melanocytes by free radicals may have a significant role in the pathogenesis of generalized vitiligo.

Alterations in plasma essential trace elements selenium, manganese, zinc, copper, and iron concentrations and the possible role of these elements on oxidative status in patients with childhood asthma

The aim of the present study is to evaluate the status of plasma essential trace element selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) concentrations and the effect of these elements on oxidative status in patients with childhood asthma. Plasma Se, Mn, Cu, and Zn concentrations were determined by atomic absorption spectrophotometry (AAS) and Fe concentrations, malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined by the colorimetric method. The plasma MDA/TAC ratio was calculated as an index of oxidative status. Plasma albumin levels were measured to determine nutritional status. Plasma Fe concentrations, MDA levels and the MDA/TAC ratio were significantly higher (p<0.001, p<0.001, and p<0.01, respectively) and Se and Mn concentrations and TAC were lower (p<0.01, p<0.05, and p<0.01, respectively) in patients when compared to the healthy subjects. Plasma Zn, Cu, and albumin levels were not found to be significantly different in patients and controls (p>0.05). There were positive relationships between plasma MDA and Fe (r=0.545, p<0.001) and TAC and Se (r=0.485, p<0.021), and a negative correlation between TAC and MDA values (r= −0.337, p<0.031) in patients with childhood asthma. However, there was no correlation between these trace elements and albumin content in patient groups. These observations suggest that increased Fe and decreased Se concentrations in patients with childhood asthma may be responsible for the oxidant/antioxidant imbalance.

Oxidative stress markers, C-reactive protein and heat shock protein 70 levels in subjects with metabolic syndrome.

Abstract Background: The metabolic syndrome is a cluster of cardiovascular risk factors and essential components of metabolic syndrome are hyperglycemia, hypertension, visceral obesity, hypertriglyceridemia and low high-density lipoprotein cholesterol. Oxidative stress plays a critical role in the pathogenesis of metabolic syndrome components and insulin resistance. The aim of this study was to investigate the role of oxidative stress, C-reactive protein and heat shock protein 70 levels in the pathogenesis of this disease. Methods: A total of 36 patients diagnosed with metabolic syndrome and 33 controls were included in the study. Malondialdehyde, carbonyl protein, C-reactive protein and heat shock protein 70 levels and xanthine oxidase and superoxide dismutase activities were measured in the serum of the subjects. Results: Mean serum malondialdehyde, carbonyl protein, C-reactive protein (p<0.01, p<0.05 and p<0.001, respectively) and xanthine oxidase activity were significantly higher (p<0.01) in serum of the patients than the control group. Superoxide dismutase activity and heat shock protein 70 levels were significantly lower (p<0.01 and p<0.05, respectively) in serum of the patients. Conclusions: These results suggest that oxidative stress parameters and components of metabolic syndrome are closely related; therefore, significant alterations may occur in the antioxidant and inflammatory status. However, further studies are required to evaluate the possible molecular mechanisms of heat shock protein 70 levels in metabolic syndrome. Clin Chem Lab Med 2008;46:785–90.

Vitamin E protects against oxidative damage caused by formaldehyde in the liver and plasma of rats.

It is well known that formaldehyde (FA) and reactive oxygen species (ROS) are cytotoxic and potentially carcinogenic. Although the individual effects of these reactants on cells have been investigated, the cytotoxicity exerted by the coexistence of FA and ROS is poorly understood. The present study was carried out to evaluate oxidant/antioxidant status and biochemical changes occurring after chronic formaldehyde toxicity in liver tissue and plasma of rats and protective effect of vitamin E (vit E) against oxidative damage. Eighteen rats were divided into three groups: (1) control rats, (2) rats treated with FA (FAt), and (3) rats treated with FA plus vit E (FAt + vit E) groups. After the treatment, the animals were sacrificed and liver tissues were removed for biochemical investigations. As a result, FA treatment significantly increased the levels of tissue malondialdehyde (MDA), protein carbonyl (PC), nitric oxide (NO) and the activity of xanthine oxidase enzyme (XO). On the other hand, FA exposure led to decrease in superoxide dismutase (SOD) and catalase (CAT) activities in liver tissues compared to control. FA caused significant decreases in total protein (TP) and albumin (ALB) whereas increases in aspartate transaminase (AST), alanine aminotransferase (AST), alkaline phosphatase (ALP) and interleukine-2 (IL-2) levels in plasma. Vit E treatment abolished these changes at a level similar to the control group. It was concluded that vit E treatment might be beneficial in preventing FA-induced liver tissue damage, and therefore have potential for clinical use.

The protective effect of nebivolol on ischemia/reperfusion injury in rabbit spinal cord.

The aim of this experimental study was to investigate whether nebivolol has protective effects against neuronal damage induced by spinal cord ischemia/reperfusion (I/R). Twenty-one rabbits were divided into three groups: group I (control, no I/R), group II (only I/R) and group III (I/R+nebivolol). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the aortic bifurcation. Seventy-two hours postoperatively, the motor function of the lower limbs was evaluated in each animal. The animals were sacrificed at 72 h, and histopathological and biochemical analyses were carried out in the lumbar spinal cords. The motor deficit scores in nebivolol group were different from I/R group at 72 h (3.25+/-0.70 vs. 1.75+/-1.28, p=0.01). I/R produced a significant increase in the superoxide dismutase (SOD), xanthine oxidase (XO), adenosine deaminase (ADA) and myeloperoxidase (MPO) activities in spinal cord tissue when compared with control group. Nebivolol treatment prevented the increase of all those enzymes activities produced by I/R. A significant decrease in spinal cord glutathione peroxidase (GSH-Px) level was seen in I/R group and nebivolol treatment prevented the decrement in the spinal cord tissue GSH-Px contents. On the other hand, I/R produced a significant increase in the spinal cord tissue malondialdehyde (MDA) and nitric oxide (NO) contents, this was prevented by nebivolol treatment. In conclusion, this study demonstrates a considerable neuroprotective effect of nebivolol on neurological, biochemical and histopathological status during periods of spinal cord I/R in rabbits.

APRI, the FIB-4 score, and Forn's index have noninvasive diagnostic value for liver fibrosis in patients with chronic hepatitis B.

Objectives The aim of this study was to evaluate the potential use of serum transforming growth factor-&bgr;1 (TGF-&bgr;1), tissue inhibitor of metalloproteinase-1 (TIMP-1), fetuin-A, and fibroblast growth factor 21 (FGF21) in the detection of liver fibrosis in patients with chronic hepatitis B (CHB). The value of the noninvasive fibrosis models – that is, the aspartate aminotransferase to platelet ratio index (APRI), the fibrosis index based on the four factors (FIB-4) score, and Forn’s index – was also examined. Materials and methods CHB patients who underwent liver biopsy for the evaluation of fibrosis were included in the study. A total of 73 patients were divided into two groups according to their METAVIR scores (F0–1, no/minimal fibrosis; F2–4, significant fibrosis). Serum levels of TGF-&bgr;1, TIMP-1, fetuin-A, and FGF21 were measured besides APRI, FIB-4, and Forn’s scores. The area under the receiver operating characteristic curve was measured for each parameter, followed by calculation of sensitivity, specificity, and positive and negative predictive values. Results APRI, FIB-4, and Forn’s index scores were significantly higher in patients with significant fibrosis (P<0.05). There was no difference between no/minimal fibrosis and significant fibrosis groups in terms of serum levels of TGF&bgr;-1, TIMP-1, fetuin-A, and FGF21 (P>0.05). The areas under the receiver operating characteristic curve for TGF-&bgr;1, TIMP-1, fetuin-A, FGF21, APRI, FIB-4, and Forn’s index were 0.445, 0.483, 0.436, 0.585, 0.662, 0.687, and 0.680, respectively. Conclusion Our results suggest that serum TGF-&bgr;1, TIMP-1, fetuin-A, and FGF21 are not useful for the assessment of the extent of liver fibrosis in CHB in this patient group. However, APRI, FIB-4, and Forn’s index have a better diagnostic value in patients with significant fibrosis than in those with no/minimal fibrosis.