Mustafa Orkmez

Increased oxidative stress and oxidative DNA damage in non-remission schizophrenia patients

Increasing evidence shows that oxidative stress plays a role in the pathophysiology of schizophrenia. But there is not any study which examines the effects of oxidative stress on DNA in schizophrenia patients. Therefore we aimed to assess the oxidative stress levels and oxidative DNA damage in schizophrenia patients with and without symptomatic remission. A total of 64 schizophrenia patients (38 with symptomatic remission and 26 without symptomatic remission) and 80 healthy volunteers were included in the study. 8-hydroxydeoxyguanosine (8-OHdG), total oxidant status (TOS) and total antioxidant status (TAS) were measured in plasma. TOS, oxidative stress index (OSI) and 8-OHdG levels were significantly higher in non-remission schizophrenic (Non-R-Sch) patients than in the controls. TOS and OSI levels were significantly higher in remission schizophrenic (R-Sch) patients than in the controls. TAS level were significantly lower and TOS and OSI levels were significantly higher in R-Sch patients than in Non-R-Sch patients. Despite the ongoing oxidative stress in patients with both R-Sch and Non-R-Sch, oxidative DNA damage was higher in only Non-R-Sch patients compared to controls. It is suggested that oxidative stress can cause the disease via DNA damage, and oxidative stress plays a role in schizophrenia through oxidative DNA damage.

Evaluation of oxidant and antioxidant status and relation with prolidase in systemic sclerosis.

SummaryPurposeSystemic sclerosis (SSc) is a disease characterized by fibrosis of the skin and organs; it is associated with diffuse fibroproliferative microangiopathy and autoimmune background. The studies have shown that the production of excessive free radicals and increased collagen synthesis by the fibroblasts play an important role in the pathophysiology of SSc. Prolidase is an important marker in collagen turnover. We aimed to compare total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and prolidase levels of SSc patients and healthy controls. We also investigated the relationship between prolidase and oxidative stress.MethodsA total of 38 SSc patients and 33 healthy volunteers were included in the study. Serum TAS, TOS, and prolidase activity were evaluated in the groups.ResultsIt was found that the TOS and OSI levels of patients were higher than those in the control group (P = 0.012 and 0.015, respectively), whereas TAS was not significantly different between groups (P = 0.451). Prolidase activity was lower in patients than in controls (P = 0.008). There was a weak correlation between prolidase and OSI in patients. It was found that TAS was lower by marginal significance in the patients with lung and gastrointestinal tract (GT) involvement than the patients without those (P = 0.067 and 0.059, respectively).ConclusionsOur data suggest that oxidative stress is increased in SSc. TAS is decreased in patients with lung and GT involvement. These results support that antioxidant treatment may be useful in SSc, especially in patients with lung and GT involvement. Antioxidant treatment may prevent organ involvement in SSc. TAS may be a marker that predicts the risk of involvement of a specific organ. In addition, prolidase may be a marker of SSc.ZusammenfassungZiel der StudieDie systemische Sklerose (SSc) ist eine Erkrankung, die durch Fibrose der Haut und der Organe gekennzeichnet ist; sie ist vergesellschaftet mit einer diffusen fibroproliferativen Mikroangiopathie und einem autoimmunen Hintergrund. Es konnte in verschiedenen Studien gezeigt werden, dass die überschießende Produktion von freien Radikalen und die gesteigerte Kollagensynthese durch Fibroblasten eine wichtige Rolle in der Pathophysiologie der SSc spielen. Prolidase ist ein wichtiger Marker des Turnovers von Kollagen. Ziel unserer Studie war es, den gesamten oxidativen Status (TOS), den gesamten antioxidativen Status (TAS), den oxidativen Stress Index (OSI) und die Serum-Konzentrationen der Prolidase bei Patienten mit SSc und bei gesunden Kontrollen zu erheben. Außerdem untersuchten wir, ob ein Zusammenhang zwischen Prolidase und oxidativem Stress besteht.Methodik38 Patienten mit SSc und 33 gesunde Freiwillige wurden in die Studie aufgenommen. Serum TAS, TOS und Prolidase-Aktivität wurden in beiden Gruppen erhoben.ErgebnisseDie TOS und OSI waren bei den Patienten höher als bei der Kontrolle (P = 0,012 beziehungsweise 0,015). Die TAS unterschied sich allerdings nicht signifikant zwischen beiden Gruppen (P = 0,451). Die Aktivität der Prolidase war bei den Patienten niedriger als bei den Gesunden (P = 0,008). Bei den Patienten bestand eine schwache Korrelation zwischen Prolidase und dem OSI. Bei den Patienten mit Beteiligung der Lunge und des Gastrointestinaltraktes (GI-Trakt) waren die TAS grenzwertig signifikant niedriger (P = 0,067 beziehungsweise 0,059) als bei den Patienten ohne Befall dieser Organe.SchlußfolgerungenUnsere Ergebnisse lassen vermuten, dass der oxidative Stress bei SSc erhöht ist. TAS ist bei Beteiligung der Lungen und des GI-traktes erniedrigt. Eine antioxidative Behandlung könnte daher bei SSc – vor allem wenn Lungen und GI-Trakt befallen sind, von Nutzen sein. Diese Behandlung könnte der Organbeteiligung vorbeugen. TAS könnte ein Marker sein, der das Risiko des Befalls eines bestimmten Organs vorhersagt. Außerdem könnte die Prolidase ein Marker der SSc sein.

The effects of oral Ginkgo biloba supplementation on radiation-induced oxidative injury in the lens of rat.

Background: The aim of this study was to evaluate the antioxidant role of Ginkgo biloba (GB) against radiation-induced cataract in the rat lens after total cranial irradiation with a single 5 Gray (Gy) dose of gamma irradiation. Materials and Methods: Twenty-four Sprague-Dawley rats were used for the experiment. The rats were randomly divided into three equal groups. Group 1 did not receive GB or irradiation (control group) but received 1-ml saline orally plus sham-irradiation. Group 2 received total cranium 5 Gy of gamma irradiation as a single dose (IR group) plus 1-ml saline orally. Group 3 received total cranium irradiation plus 40 mg/kg/day GBE (IR plus GBE group). Biochemical parameters measured in murine lenses were carried out using spectrophotometric techniques. Results: Lens total (enzymatic plus non-enzymatic) superoxide scavenger activity (TSSA), non-enzymatic superoxide scavenger activity (NSSA), glutathione reductase (GRD), and glutathione-S- transferase (GST) activities significantly increased in the IR plus GBE groups when compared with the IR group. However, TSSA, GRD and GST activities were significantly lower in the IR group when compared with the control group. Lens xanthine oxidase (XO) activity in the IR group significantly increased compared to that of both the control and IR plus GBE groups. Conclusion: GBE has clear antioxidant properties and is likely to be a valuable drug for protection against gamma-irradiation and/or be used as an antioxidant against oxidative stress.

Urotensin Inhibition with Palosuran Could Be a Promising Alternative in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive and a life-threatening disease with its high morbidity and mortality ratios. On searching for new shining targets in pathogenesis, we noticed, in our previous studies, urotensin-II (UII) in systemic sclerosis with potent angiogenic and pro-fibrotic features. Owing to the mimicking properties of UII with endothelin-1 (ET1), we attempted to investigate the effect of palosuran in a PAH rat model. Thirty rats were randomly divided into three groups, with each group comprising 10 rats: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran group) received subcutaneous MCT and palosuran. Serum UII, ET1, transforming growth factor-β1 (TGF-β1) levels, pulmonary arteriolar pathology of different diameter vessels, and cardiac indices were evaluated. The ET1, TGF-β1, and UII levels were significantly diminished in the treatment group, similar to the controls (p < 0.001). Right ventricular hypertrophy index and mean pulmonary arterial pressure scores were also significantly reduced in the treatment group (p = 0.001). Finally, in the 50–125-μm diameter arterioles, in contrast to Groups 3 and 1, there was a statistically significant thickness (p < 0.01) in the arteriolar walls of rats in Group 2. The treatment effect on arteries of more than 125-μm diameters was found to be valuable but not significant. Owing to its healing effect on hemodynamic, histological, and biochemical parameters of MCT-induced PAH, palosuran as an antagonist of UII might be an optional treatment alternative for PAH.

Zinc administration modulates radiation-induced oxidative injury in lens of rat

Background: The aim of this study was to evaluate the antioxidant role of zinc (Zn) against radiation-induced cataract in the rat lens after total cranial irradiation with a single 5 Gray (Gy) dose of gamma irradiation. Materials and Methods: Twenty-one Sprague-Dawley rats were used for the experiment. The control group did not receive Zn or irradiation but received 1-ml saline orally plus sham-irradiation. The irradiation (IR) group received 5 Gy gamma irradiation to the total cranium as a single dose plus 0.1 ml physiological saline intraperitoneally. The IR plus Zn group received irradiation to total cranium plus 10 mg/kg/day Zn intraperitoneally. Biochemical parameters measured in rat lenses were carried out using spectrophotometric techniques. Results: Lens total (enzymatic plus non-enzymatic) superoxide scavenger activity (TSSA), glutathione reductase (GRD), and glutathione-S-transferase (GST) activities significantly increased in the IR plus Zn groups when compared with the IR group. However, TSSA, GRD and GST activities were significantly lower in the IR group when compared with the control group. Lens non-enzymatic superoxide scavenger activity (NSSA) in the IR plus Zn group was significantly increased compared to that of the IR group. Lens xanthine oxidase (XO) activity in the IR group significantly increased compared to that of both the control and IR plus Zn groups. Conclusion: Zn has clear antioxidant properties and prevented oxidative stress by scavenging free radicals generated by ionizing radiation in rat lenses.

Evaluation of oxidative metabolism and oxidative DNA damage in patients with obsessive–compulsive disorder

There are limited published data about the role of oxidative stress in the pathophysiology of obsessive–compulsive disorder (OCD). In addition, oxidative stress and oxidative DNA damage have not been investigated together in OCD. In this study, we aimed to evaluate oxidative stress and oxidative DNA damage in patients with OCD.

An assessment of oxidant/antioxidant status in patients with snake envenomation

Objective The aim of this study is to investigate the antioxidant status (TAS), oxidant status (TOS) and oxidative stress index (OSI) in patients with snake envenomation and to learn more about the pathophysiology of snake envenomation. Method Between May 2009 and October 2010, 47 patients were admitted to our emergency department with snake bites, and as a control group 20 healthy volunteers were enrolled in this study. Serum, plasma, and erythrocyte components were prepared for all patients on admission and at the control after 1 month. Serum TOS/TAS levels were measured. Results No correlation was observed among age, gender and the levels of TAS, TOS and OSI. TAS, TOS and OSI levels were higher in snake envenomation patients upon arrival at the emergency department than in the healthy control group. Upon admission, all levels of patients with snake envenomation were higher than the control levels taken after 1 month. Conclusions Serum TAS, TOS and OSI levels increase in snake envenomation patients. The results obtained in this study indicate that the snake bite was associated with a shift to an oxidative state, and oxidative stress plays an important role in the pathophysiology of snake envenomation.

Oxidative imbalance and anxiety in patients with sleep bruxism.

OBJECTIVE We evaluated the relationship among sleep bruxism (SB), antioxidant/oxidant status, and anxiety level to determine whether antioxidant/oxidant status may be used as a biological marker of SB. STUDY DESIGN Thirty-three SB and 32 healthy patients of similar age, sex, and body mass index were enrolled, venous blood was collected, and anxiety scores were determined. Plasma samples were analyzed for total oxidant status, antioxidant status, and oxidative stress index. RESULTS In 2 of the 3 assays performed, SB patients exhibited an oxidative imbalance. A higher anxiety score was observed with SB (P < 0.05). CONCLUSIONS These results show that oxidant/antioxidant imbalance may be related to SB, either pathophysiologically or as an outcome of the condition. Further biochemical studies could prove useful in determining the importance of antioxidant drugs in the treatment of SB.

Relationship between soluble intercellular adhesion molecules and attention-deficit/hyperactivity disorder

Objective Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-oneset psychiatric disease, characterized by excessive overactivity, inattention, and impulsiveness. In recent studies, it is emphasized that inflammation may have a role in ADHD. In this study, we aimed to investigate whether there are associations between ADHD and serum levels of soluble intercellular adhesion molecules (s-ICAMs) which have important role in inflammatory diseases. We also measured the levels of these molecules after treatment with oros-methylphenidate. Methods Twenty-five patients diagnosed with ADHD according to Diagnostic and Statistical Manual of Mental Disorders-IV-TR criteria and 18 healthy volunteer controls were included in this study. The levels of sICAMs were measured in the serum of the patients and healthy volunteers by ELISA kit as described. Results The levels of sICAM-1 and sICAM-2 were significantly higher in patients compared with controls. The level of sICAM-2 was decreased significantly in group treated with oros-methylphenidate. Conclusions This is the first study pointing out the relationship between sICAMs and ADHD. The changes in sICAM-2 level may have a role in the effect mechanism of oros-methylphenidate, used for the treatment of ADHD.

New molecule in the etiology of schizophrenia: Urotensin II

Urotensin II (U‐II) is a cyclic peptide that was first isolated from the caudal neurosecretory system of goby fish. U‐II receptors were detected in the vascular endothelium, brain and kidney cortex. Urotensin is by far the most powerful vasoconstrictor identified. U‐II molecules were previously isolated from the brain of rats and were shown to have an impact on rat behavior. The aim of the present study was to measure the level of U‐II molecule in schizophrenia patients and to investigate whether the U‐II level is associated with the etiology of schizophrenia.