Efkan Uz

The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. The possible role of oxidant/antioxidant imbalance.

There is great evidence in recent years that oxygen free radicals play an important role in the pathophysiology of schizophrenia. The present study was performed to assess the changes in plasma nitric oxide (NO) and thiobarbituric acid-reactive substances (TBARS) levels, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and xanthine oxidase (XO) activities in schizophrenic patients compared to age- and sex-matched normal controls. A hundred patients with schizophrenia and 51 healthy volunteers were included in the study. XO, SOD, and GSH-Px activities as well as NO and TBARS levels were estimated by standard biochemical techniques in the plasma of normal healthy controls and schizophrenia patients. In schizophrenia, increased plasma XO activity (P < .0001) and NO levels (P < .0001), decreased SOD activity (P < .0001), and unchanged GSH-Px activity were detected compared to control group. Plasma TBARS levels were increased in schizophrenic patients (P < .01), especially in the residual subtype. TBARS levels in nonsmoker schizophrenic patients were found to be higher than nonsmoker controls. Although TBARS levels in both patients and controls were found to be higher in smokers as compared to nonsmokers, it was not statistically significant. No effects of duration of the illness, gender, and low and high dose of daily neuroleptic treatment equivalent to chlorpromazine on oxidant and antioxidant parameters were observed. Because the dose and the duration of treatment with drugs have no influence on the results, it can be interpreted that the findings are more likely to be related mainly to the underlying disease. These findings indicated a possible role of increased oxidative stress and diminished enzymatic antioxidants, both of which may be relevant to the pathophysiology of schizophrenia. On the other hand, increased NO production by nitric oxide synthetases (NOSs) suggests a possible role of NO in the pathophysiological process of schizophrenia. These findings may also suggest some clues for the new treatment strategies with antioxidants and NO synthase (NOS) inhibitors in schizophrenia.

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.

The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia/reperfusion injury in rabbits.

OBJECTIVE Oxygen-derived free radicals have been implicated in the pathogenesis of spinal cord neuronal injury after both trauma and ischemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, exhibits antioxidant properties. This experimental study was designed to determine the effect of CAPE on ischemia-reperfusion of spinal cord in rabbits. METHODS Forty-one New Zealand white rabbits were used in the study. The animals undergone aortic occlusion were divided into three groups each consisting of 11 rabbits: methylprednisolone (MP), CAPE, and control. CAPE 10 micromol/kg, methyl prednisolone (MP) 30 mg/kg or similar dose saline were injected intraperitoneally before surgical intervention. Animals were subjected to 21 min of cross-clamp time. At the end of occlusion time, the clamps were removed and restoration of the blood flow was verified visually. Animals in sham group (n = 8) underwent a surgical procedure similar to the other groups but the aorta was not occluded. Neurological status was scored by assessment of hindlimb motor function deficit. RESULTS The scores in CAPE group was different from control groups at 48 h (3.91+/-0.5 vs. 2.91+/-0.7; P = 0.0013). Spinal cord specimens were obtained to determine the tissue levels of malondialdehyde, superoxide dismutase, catalase, and histological changes. Malondialdehyde levels in control group were increased significantly when compared to sham group (124.22+/-24.36 and 41.92+/-10.08 nmol/g wet tissue, P = 0.0003). MDA levels in the CAPE group were lower than MP group and differences between the two groups were statistically significant (56.77+/-15.265 and 107.74+/-19.31 nmol/g wet tissue, P = 0.0001). We did not observe additional tissue injury in CAPE group when compared to control group. SOD and CAT activities were not concordant in all the groups. CONCLUSIONS These results suggest that CAPE may be an available agent to protect the spinal cord from ischemia-reperfusion injury.

Possible role of nitric oxide and adrenomedullin in bipolar affective disorder.

Nitric oxide (NO) has been implicated to play a role in the pathogenesis of depressive disorders. Adrenomedullin (AM) induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of NO. AM immune reactivity is present in the brain, consistent with a role as neurotransmitter. Therefore, it is suggested that these two molecules may play a role together in the brain. We aimed to examine AM and NO in bipolar affective disorder (BPAD). Forty-four patients with BPAD and 21 healthy control subjects were included in this study. DSM-IV diagnosis of bipolar affective disorder (type I, manic episodes) was independently established by two psychiatrists and the Turkish version of the Bech-Rafaelson Mania Scale was administered. Also, a semistructured form was used to ascertain several sociodemographic and clinical variables of the patients. AM and NO were studied in plasma. The mean value of plasma NO levels in the BPAD group of 46.58 ± 13.97 µmol/l was significantly higher than that of controls (31.81 ± 8.14 µmol/l) (z = –4.15, p = 0.000). Mean plasma AM levels were found to be increased in patients with BPAD (35.13 ± 5.26 pmol/l) compared to controls (16.22 ± 3.02 pmol/l) (z = –6.16, p = 0.000). AM levels of BPAD patients were approximately 2-fold higher than controls. AM levels were positively correlated with the duration of hospitalization for the current episode and negatively correlated with the total duration of illness. Both NO and AM may have a pathophysiological role in BPAD (type I, manic episodes) and the clinical symptomatology and prognosis of BPAD.

Testicular nitric oxide levels after unilateral testicular torsion/detorsion in rats pretreated with caffeic acid phenethyl ester

Abstract Nitric oxide (NO) plays an important role in modulating blood flow in normal and in several pathological conditions, and its levels seem to change with ischemia–reperfusion injuries. Caffeic acid phenethyl ester (CAPE), an active component of propolis, exhibits antioxidant properties. This experimental study was designed to determine the changes in NO levels and the effect of CAPE on NO levels after testicular torsion/detorsion in rats. Thirty-five adult male albino rats were divided into four groups: sham operation (n=8), torsion (n=9), saline/detorsion (n=9), and CAPE/detorsion (n=9). Rats in the sham operation group were killed after the testes were handled without torsion. Rats in the torsion group were killed after 720° clockwise testicular torsion for 2 h. CAPE was administered 30 min before detorsion in the CAPE/detorsion group and saline was administered in the saline/detorsion group. After 4 h of testicular detorsion in both of these groups, the rats were killed and bilateral orchiectomy was performed to determine the tissue levels of NO. The level of NO in the torsion group (113.77 ± 33.18 nmol/g protein) was significantly higher than that of the sham operation group (64.53 ± 29.64 nmol/g protein). In the saline/detorsion group, the NO level (31.26 ± 12.58 nmol/g protein) was significantly lower than in the torsion and sham operation groups. CAPE administration in the CAPE/detorsion group seemed to raise the NO level (72.63 ± 23.87 nmol/g protein) above the level of the sham operation group. Contralateral testes were not affected by the torsion/detorsion processes performed on the ipsilateral testes. These results show that NO levels increase with torsion and decrease with detorsion. CAPE administration seems to increase tissue NO levels and this may be important for protecting the testes from torsion/detorsion injuries.

The possible pathophysiological role of plasma nitric oxide and adrenomedullin in schizophrenia

Evidence is accumulating for a possible role of nitric oxide (NO) in schizophrenia. Adrenomedullin (AM) induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of NO. AM immune reactivity is present in the brain consistent with a role as neurotransmitter. We aimed to examine plasma levels of nitrite (a metabolite of NO) and AM in schizophrenic patients. Eighty-two patients with schizophrenia and 21 healthy control subjects were included in this study. DSM-IV diagnosis of chronic schizophrenia was established on the basis of independent structured clinical interviews and review of records by two qualified psychiatrists which included the Brief Psychiatric Rating Scale (BPRS), The Scale for the Assessment of Negative Symptoms (SANS) and The Scale for the Assessment of Positive Symptoms (SAPS). Total nitrite and AM have been studied in plasma. The mean values of plasma nitrite and AM levels in schizophrenic group were significantly higher than control values, respectively (P=0.03, P<0.0001). AM levels of schizophrenic patients were three fold higher than controls. In correlation analyses, there were statistically significant positive correlations between AM level and SAPS-delusion subscale (r=0.27, P=0.04); SAPS-bizarre behavior subscale (r=0.28, P=0.03) and SAPS-total (r=0.36, P=0.005). There is no correlation between total nitrite and AM levels (r=0.11, P=0.31). Both NO and AM may have a pathophysiological role in schizophrenia, and clinically symptomatology and prognosis of schizophrenia. This subject needs further study including treatment response and subtypes of schizophrenia.

Plasma superoxide dismutase activity and malondialdehyde level correlate with the extent of acute appendicitis

Abstract Although the mechanism of acute appendicitis (AA) is partly understood, the progression following the onset of inflammation has not yet been clarified. To determine oxidative activities in the plasma of patients with AA, superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured in samples from 31 patients diagnosed as having AA and 10 otherwise healthy children with inguinal pathologies. The patients with AA were divided into three subgroups: acute focal (AFA) (n=8), acute suppurative (ASA) (n=9), and acute perforated appendicitis (APA) (n=14), according to the intraoperative findings and histopathologic examination. SOD and MDA were compared statistically between these subgroups and between them and the control group. Additionally, mean leukocyte counts of each group were determined and the differences between the groups were evaluated. Both SOD and MDA were significantly higher in the ASA and APA groups compared to controls and AFA group. The mean leukocyte numbers of the ASA and APA groups were significantly higher compared to the AFA group. Based to these results, it may be speculated that oxygen free radicals (OFR) may play an important role in the extent of AA. To prevent the hazardous effects of OFR, the organism may increase SOD and other antioxidant enzyme levels and/or activities.