Sadık Söğüt

Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism

BACKGROUND There is evidence that oxygen free radicals play an important role in the pathophysiology of many neuropsychiatric disorders. Although it has not been investigated yet, several recent studies proposed that nitric oxide (NO) and other parameters related to oxidative stress may have a pathophysiological role in autism. METHODS We assessed the changes in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and thiobarbituric acid-reactive substances (TBARS) levels in plasma as well as NO levels in red blood cells (RBC) in patients with autism (n=27) compared to age- and sex-matched normal controls (n=30). RESULTS In the autistic group, increased RBC NO levels (p<0.0001) and plasma GSH-Px activity (p<0.0001) and unchanged plasma TBARS levels and SOD activity were detected. CONCLUSIONS These findings indicate a possible role of increased oxidative stress and altered enzymatic antioxidants, both of which may be relevant to the pathophysiology of autism.

Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia

In order to examine antioxidant status and lipid peroxidation in schizophrenia patients, activities of three free radical scavenging enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)), and the level of thiobarbituric acid-reactive substances (TBARS) as an index of lipid peroxidation have been studied in red blood cells. Schizophrenic patients were divided into three groups (disorganized (n = 21), paranoid (n = 26) and residual types (n = 18)) to determine differences between subgroups. SOD, CAT and GSH-Px activities in the control group were found to be 1461.0 ± 248.6 U g−1 Hb, 148.2 ± 59.3 k g−1 Hb and 25.87 ± 4.25 U g−1 Hb, respectively. We found no significant differences in SOD activities between study and control groups. There was a significant increase in SOD activity in the residual group compared to the paranoid group (P < 0.005). CAT activity was found to be increased in disorganized (148%), paranoid (147%), and residual (165%) groups compared to the control group. GSH-Px activity was markedly increased in the study groups except the paranoid group. Statistically significant (3–4 fold) increases in TBARS levels of red blood cells were found in all the study groups. It is proposed that antioxidant status may be changed in schizophrenia and thus may induce lipid peroxidation. Therefore, oxidative stress may have a pathophysiological role in all the subtypes of schizophrenia.

Potential role of dietary ω-3 essential fatty acids on some oxidant/ antioxidant parameters in rats' corpus striatum

Omega-3 (omega-3) is an essential fatty acid (EFA) found in large amounts in fish oil. It contains eicosapentaenoic acid and docosahexaenoic acid (DHA). DHA is one of the building structures of membrane phospholipids of brain and necessary for continuity of neuronal functions. Evidences support the hypothesis that schizophrenia may be the result of increased reactive oxygen species mediated neuronal injury. Recent reports also suggest the protective effect of omega-3 EFA against neuropsychiatric disorders including schizophrenia. This study proposed to assess the changes in antioxidant enzyme and oxidant parameters in the corpus striatum (CS) of rats fed with omega-3 EFA diet (0.4g/kg/day) for 30 days. Eight control rats and nine rats fed with omega-3 were decapitated under ether anesthesia, and CS was removed immediately. Thiobarbituric acid-reactive substances (TBARS) and nitric oxide (NO) levels as well as total superoxide dismutase (t-SOD) and xanthine oxidase (XO) enzyme activities in the CS were measured. Rats treated with omega-3 EFA had significantly lower values of TBARS (P<0.001), NO (P<0.002) and XO (P<0.005) whereas higher values of t-SOD enzyme activity (P<0.002) than the control rats. These results indicate that omega-3 EFA rich fish oil diet reduces some oxidant parameters in CS. This may be revealed by means of reduced CS TBARS levels as an end product of lipid peroxidation of membranes in treated rats. Additionally, reduced XO activity and NO levels may support this notion. On the other hand, although the mechanism is not clear, omega-3 EFA may indirectly enhance the activity of antioxidant enzyme t-SOD. Taken together, this preliminary animal study provides strong support for a therapeutic effect of omega-3 EFA supplemented to classical neuroleptic regimen in the treatment of schizophrenic symptoms and tardive dyskinesia.

Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats.

The effect of oral erdosteine on tissue malondialdehyde (MDA) and nitric oxide (NO) levels, and catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are investigated in the cisplatin model of acute renal failure in rats. A single dose of cisplatin caused kidney damage manifested by kidney histology as well as increases in plasma creatinine and blood urea nitrogen (BUN) levels. Treatment with free radical scavenger erdosteine attenuated increases in plasma creatinine and BUN, and tissue MDA and NO levels, and provided a histologically-proven protection against cisplatin-induced acute renal failure. Erdosteine also reduced depletion in the tissue CAT, GSH-Px, and SOD activities. These results show that erdosteine may be a promising drug for protection against cisplatin-induced nephrotoxicity. However, further studies with different doses of erdosteine are warranted for clarifying the issue.

Serum nitric oxide, catalase, superoxide dismutase, and malondialdehyde status in patients with ankylosing spondylitis

In this study, serum antioxidant and oxygen derived free radical status of patients with ankylosing spondylitis (AS) was investigated and compared with that of age- and sex-matched healthy controls. The relationship of these parameters to disease activity indices was also examined. Thirty patients with AS not currently under disease-modifying antirheumatic drug (DMARD) treatment (e.g., sulfasalazine or methotrexate) (15 active and 15 inactive) and 16 age- and sex-matched healthy controls were included in the study. Catalase (EC 1.11.1.6), total (Cu-Zn and Mn) superoxide dismutase (SOD) (EC 1.15.1.1) activities, and malondialdehyde (MDA), nitrite (NO2-), and nitrate (NO3-) levels as indices of nitric oxide (NO) production were evaluated using appropriate methods. There was no statistically significant difference found in SOD activity or NO and MDA levels between active and inactive patients. Inactive patients showed no significant difference in all the measured oxidant/antioxidant parameters when compared to healthy controls. Active patients had significantly higher levels of MDA and catalase enzyme activity (P=0.002 and P=0.007, respectively). There was no significant correlation between oxidant/antioxidant parameters and disease activity, C-reactive protein, erythrocyte sedimentation rate, or Bath Ankylosing Spondylitis Disease Activity Index (CRP, ESR, or BASDAI) in either group, except catalase enzyme activity, which had a significant correlation with CRP and ESR levels in active patients (r=0.69 and P=0.004, r=0.52 and P=0.04, respectively). Our results indicate that oxidative stress and lipid peroxidation are accelerated in untreated patients with active AS. Serum catalase activity may be closely related to disease activity. In this regard, we underscore the likely benefit of some therapeutic interventions including high-potential antioxidants that will potentiate the antioxidant defense mechanism and reduce peroxidation in the management of AS.

The activities of liver adenosine deaminase, xanthine oxidase, catalase, superoxide dismutase enzymes and the levels of malondialdehyde and nitric oxide after cisplatin toxicity in rats: protective effect of caffeic acid phenethyl ester.

The aim of this experimental study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, on cisplatin-induced hepatotoxicity through adenosine deaminase (AD), xanthine oxidase (XO), catalase (CAT), superoxide dismutase (SOD) activities and malondialdehyde (MDA) and nitric oxide (NO) levels in liver tissue of rats. Wistar albino rats were divided into three groups: control group (n-6), cisplatin group (n-9) and CAPE+cisplatin group (n-8). All the chemicals used were applied intraperitoneally. Spectrophotometric methods were used to determine the activities of the above-mentioned enzymes in the liver tissue. NO level and XO activity were found to be increased in the cisplatin group compared to the control group. NO level was found to be decreased in the cisplatin+CAPE group in comparison with the cisplatin group. There was no significant change in the activity of XO between the cisplatin and cisplatin+CAPE groups. The activity of SOD was lower in the cisplatin group than both the control and cisplatin+CAPE groups. There was no significant change in the activity of CAT between the control and cisplatin groups. CAT activity was increased in the cisplatin+CAPE group compared to the cisplatin group. The AD activity and MDA level remained unchanged in all groups. The results obtained suggested that CAPE significantly attenuated the hepatotoxicity as an indirect target of cisplatin in an animal model of cisplatin-induced nephrotoxicity.

Androgen Status of the Nonautoimmune Dry Eye Subtypes

Purpose: To evaluate androgen levels of patients diagnosed with nonautoimmune dry eye, either with meibomian gland dysfunction (MGD) or without MGD (non-MGD), and normal control subjects. This is a prospective, comparative, case-control study. Methods: Sixty-four (32 men and 32 women) subjects were enrolled for each of the three diagnostic groups. All dry eye patients were symptom positive. Nonfasting testosterone (T), sex hormone-binding globulin, serum albumin, dehydroepiandrosterone (DHEA), and DHEA sulphate levels of all study participants were determined using either automated immunoenzymatic assay, or standard radioimmunoassay. Analysis of variance was used to compare androgen levels among the three diagnostic groups in a gender-based design, followed by post-hoc multiple comparisons with the Tukey honestly significant difference test. Results: Mean T levels in men and women of the three diagnostic groups were not significantly different (p = 0.808, p = 0.156, respectively; ANOVA). Statistical analyses of the three diagnostic groups revealed a significant difference for men and women in bioavailable T levels (p = 0.002, p = 0.014, respectively; ANOVA), DHEA levels (p = 0.009, p = 0.004, respectively; ANOVA), and DHEA sulphate levels (p = 0.001, p = 0.001, respectively; ANOVA), whereas there was no statistically significant difference between non-MGD dry eye patients and controls for any of the measured androgen levels according to the post-hoc tests. Conclusion: This study demonstrates that the androgen pool of nonautoimmune dry eye patients with MGD is significantly depleted compared with that of non-MGD and control cases.

Comparison of Serum Nitric Oxide, Malondialdehyde Levels, and Antioxidant Enzyme Activities in Behçet’s Disease with and without Ocular Disease

Objective: The pathogenesis of Behçet’s disease (BD) may be related to excessive production of reactive oxygen species, activated neutrophils, and T lymphocytes. The goal of this prospective study was to investigate whether there is any relationship among the oxidant/antioxidant system and nitric oxide (NO) and malondialdehyde (MDA) levels in patients with BD and its subtypes: complete Behçet’s disease (CBD) and incomplete Behçet’s disease (ICBD), with or without ocular disease. Methods: Thirty-two patients and 26 age- and sex-matched healthy control subjects were evaluated for NO and MDA levels and antioxidant enzyme activities. The patients with BD were divided into two subgroups: those with and without ocular disease. Twelve patients with CBD and 4 patients with ICBD had ocular disease. The serum NO level was determined by Griess reaction. The MDA level was detected by thiobarbituric acid reaction. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in serum were analyzed with spectrophotometric methods. Results: Increased MDA levels but decreased GSH-Px activities in plasma were observed in BD patients with all subtypes, as compared with controls. Concerning the presence of ocular disease and the subtype (CBD or ICBD) compared with each other, there were no significant differences in MDA or NO serum levels and SOD or GSH-Px enzyme activities. Conclusions: Serum NO levels and SOD enzyme activities were not significantly changed in patients with BD and its subtypes; however, a remarkable decrease of GSH-Px enzyme activity and increase of MDA levels were found.

Protective effects of omega-3 essential fatty acids against formaldehyde-induced cerebellar damage in rats

This study aimed to investigate changes in the cerebellum of formaldehyde-exposed rats and the effects of omega-3 fatty acids on these changes. The study involved 21 male Wistar-Albino rats which were divided into three groups. The rats in Group I comprised the control group. The rats in Group II were injected with intraperitoneal 10% formaldehyde every other day. The rats in Group III received omega-3 fatty acids daily while exposed to formaldehyde. At the end of the 14-day experimental period, all rats were killed by decapitation and the cerebellum removed. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), xanthine oxidase (XO), and malondialdehyde (MDA) levels were determined in cerebellum specimens by using spectrophotometric methods. In our study, levels of SOD and CAT were significantly decreased, and GSH-Px, XO, MDA levels were significantly increased in rats treated with formaldehyde compared with those of the controls. Whereas, it was seen that there was an increase in SOD and CAT enzyme activities and decrease in MDA, XO, and GSH-Px levels in rats administered to omega-3 fatty acids with exposure of formaldehyde. It was determined that exposure of formaldehyde increased free radicals in cerebellum of rats and this increase was prevented by administration of omega-3 fatty acids.

The activities of serum adenosine deaminase and xanthine oxidase enzymes in Behcet's disease.

BACKGROUND Adenosine deaminase (AD) and xanthine oxidase (XO) are enzymes of purine catabolism that catalyze the conversion of adenosine to inosine, deoxyadenosine to deoxyinosine, hypoxanthine to xanthine and xanthine to uric acid, respectively. AD is known to be an important enzyme in the maturation and function of T lymphocytes. The aim of this prospective study was to evaluate whether there are changes in serum AD activity as an index of T lymphocyte function in Behcets disease (BD) which is known as having T cell-mediated immune response. METHODS A total of 32 patients and 26 sex- and age-matched healthy control subjects were analysed for AD and XO activities. The patients with BD were divided into two subgroups: BD with and without eye lesions. Twelve patients with complete BD and four patients with incomplete BD had eye complications. AD and XO activities in serum were measured with spectrophotometric methods. RESULTS There was a remarkable increase in AD activity and moderate increase in XO in patients with BD compared to controls indicating T cell activation and increased maturation. Serum AD activity of complete BD was higher than that of incomplete BD. There was no difference in XO activity between the subgroups of BD. Significant positive correlation was found between AD and XO in BD, although there was no correlation in control group. CONCLUSIONS The results indicate that increased AD and XO activities may provide an additional benefit for the diagnosis of BD and subtyping of the disease as having eye complication or not and complete and incomplete BD. Further studies are needed to bring to light the exact mechanism of AD and XO activity elevation.