Fikret Ozugurlu

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.

Increased Nitric Oxide Production in the Spermatic Vein of Patients with Varicocele

Objective: To define the level of nitric oxide (NO) in the spermatic vein of patients with varicocele and its relation with male infertility.Materials and Methods: Following physical and color Doppler ultrasonographic examination, whole blood samples were drawn from a peripheral vein and a dilated varicocele vein from fourteen patients with clinically palpable varicocele (G2–3) before ligation. NO levels in the serum were determined as total nitrite by Greiss reaction and results were compared with Mann–Whitney U test.Results: NO levels in the internal spermatic vein were 36.05 ± 8.92 μmol/l, compared to 19.41 ± 4.12 μmol/l in the peripheral vein and the difference was statistically significant (p < 0.01).Conclusion: In view of our results, increased NO levels in the dilated varicocele vein might be responsible for spermatozoa dysfunction.

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.

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.

Levels of Iron, Zinc, and Copper in Aqueous Humor, Lens, and Serum in Nondiabetic and Diabetic Patients Their Relation to Cataract

The purpose of this study was to investigate iron (Fe), zinc (Zn), and copper (Cu) levels of aqueous humor, lens, and serum in nondiabetics and diabetics and to determine the effects of diabetes on Fe, Zn, and Cu contents in the lens. Fe, Zn, and Cu contents of aqueous humor, lens, and serum samples of 19 patients (9 nondiabetic patients with a mean age of 62.3±5.4 yr, and 10 diabetic patients with a mean age of 59.5±5.9 yr) were analyzed by atomic absorption spectrometry using a prospective study design. The lens levels of Cu in diabetic patients were significantly higher compared with nondiabetic patients (p=0.02); however; there was no difference in the other elements (Zn, Fe; p=0.28, p=0.74, respectively). The levels of Fe, Zn, and Cu in the aqueous humor and serum of diabetic patients were not found to be statistically significant when compared to nondiabetics (p=0.46, p=0.11, p=0.18, and p=0.22, p=0.43, p=0.72, respectively). These results demonstrate that increased Cu content of the lens presumably has a greater association with the development of lens opacification in diabetics than Zn and Fe content.

Comparison of the effects of troxerutin and heparinoid on flap necrosis

We aimed to assess the effects of local troxerutin and heparinoid (HEP) treatments in a model of flap necrosis. Three groups of Wistar albino rats, each comprising 10 animals were used. A cranially based 6x3-cm full-thickness random-pattern skin flap was raised and sutured to the same area in each model. The control group was treated daily with normal saline, the second with topical HEP and the third with topical troxerutin. The amount of flap necrosis was measured in all groups by the end of the seventh day. Flap tissues were excised for histological analysis and evaluation of the expression of vascular endothelial growth factor (VEGF) levels. Assessment of the blood levels of nitric oxide was also performed in each animal by cardiac puncture. The mean area of flap necrosis was 110.6mm(2) in the control, 39.44 mm(2) in the troxerutin and 47.11 mm(2) in the heparinoid-treated rats. The treatment arms exhibited significant reduction in areas of flap necrosis, compared with the control group (p<0.001), but it was similar among treatment groups (p=0.60). The rates of fibroblast proliferation were decreased in control group as compared to HEP and troxerutin arms (p<0.001). The mean level of collagen density, collagen organisation, granulation tissue and demarcation were similar in all rats. Measurement of VEGF expression did not show any significant difference between the groups (p=0.30). Nitric oxide levels were significantly higher in control rats, as compared to treatment groups (p<0.0001), but were similar in treatment arms (p=0.45). Our results suggest that troxerutin and HEP effectively reduce the flap necrosis and improve flap survival. The observed effects might be due to their anti-oedematogenic, radical-scavenging, antioxidant effects and supportive activities on capillary permeability and transudation.

The effects of chronic exposure to ethanol and cigarette smoke on the formation of peroxynitrite, level of nitric oxide, xanthine oxidase and myeloperoxidase activities in rat kidney

The aim of this study was to investigate the effects of chronic ethanol intake and cigarette smoke exposure on rat kidney. The animals were divided into four experimental groups: (1) the control group (C), (2) the ethanol group (E), (3) the cigarette smoke group (CS), and (4) the cigarette smoke plus ethanol group (CS+E). Rats in E, CS and CS+E groups were treated with ethanol and/or cigarette smoke for 6 months. The animals were killed and the kidneys were removed to determine the activity of xanthine oxidase (XO), myeloperoxidase (MPO) and the levels of nitric oxide (NO). Histopathological and immunohistochemical analysis were performed in kidney tissues. The activity of XO/g protein were 2.8 ± 0.3, 5.2 ± 0.3, 3.2 ± 0.1, and 7.4 ± 0.7 U for C, E, CS and CS+E groups, respectively. In groups E, and CS+E, the XO values were significantly higher than in group C (P < 0.05). The increase in XO activity of CS was not significantly different from group C (P > 0.05). There was a significant increase in XO activity of group CS+E as compared to CS and E groups (P < 0.05), and also a significant difference in XO activity between E and CS was observed (P < 0.05). The activity of MPO/g protein were 13.5 ± 0.6, 16.2 ± 1.1, 14.7 ± 1.1, 23.8 ± 0.9 U for C, E, CS, and CS+E groups, respectively. While MPO activity of kidneys from group CS+E were significantly higher as compared to C, CS, and E groups (P < 0.05), there was no significant difference among the groups of C, CS, E (P > 0.05). The levels of NO/g wet tissue were 347.7 ± 8.5, 261.1 ± 4.8, 329.8 ± 5.6, and 254.2 ± 3.8 nmol for C, E, CS, and CS+E groups, respectively. In groups of E and CS+E, the NO values were significantly lower than that of group C animals (P < 0.05). Although we detected lower NO levels in the E and CS+E groups than in CS group (P < 0.05), a significant difference in NO levels between CS+E and E groups was not observed. In the histopathological analysis of the kidney slices, severe degenerations in kidney tissues of group CS, E, CS+E were observed. Generally, the histological changes in kidney of CS+E and E groups were more severe than those observed in CS alone. While we observed a strong immunoreactivity for anti-nitrotyrosine antibody in kidneys of group CS+E, examination of sections from rat kidneys in group E revealed moderate staining. On the other hand, group CS had very little immunostaining. There was no immunostaining in group C.We concluded that chronic ethanol administration and cigarette smoke exposure may cause oxidative and nitrosative stress which lead to rat kidney damage.