Correlation analysis confirms differences in antioxidant defence in the blood of types I and II schizophrenic male patients treated with anti-psychotic medication

The activities of antioxidant defence enzymes were determined in erythrocytes isolated from types I and II schizophrenic male patients and from healthy controls. Significant differences in superoxide dismutase (SOD) activity (type I: 3284 +/- 577; type II: 2959 +/- 697 compared with controls: 3778 +/- 577; analysis of variance (ANOVA) P<0.001), catalase (CAT) activity (type I: 17.8 +/- 1.8 compared to type II: 19.2 +/- 1.5 and both compared with controls: 19.2 +/- 1.5; ANOVA P<0.05). glutathione peroxidase (GSH-Px) activity (controls: 17.8 +/- 2.3; type I: 13.9 +/- 2.9 and type II: 11.6 +/- 1.9; ANOVA P<0.001) as well as in glutathione reductase (GR) activity (controls: 5.0 +/- 0.8; type I: 4.3 +/- 0.9 and type II: 4.5 +/- 0.8; ANOVA P<0.01) were apparent. Correlation analysis of antioxidant defence enzymes showed significant negative correlation between GSH-Px and CAT activities (P<0.01) in type I patients. In type II patients, GSH-Px activity was significantly positively correlated with GR (P<0.01). Canonical discriminant analysis separated type I and type II patients from controls (and among each other) with a high degree of certainty according to the overall group composition of antioxidant defence enzymes. Our results indicate differences in the composition of antioxidant defence between controls and antipsychotic treated type I and type II patients with a possible negative feedback influence on the pathological process, which could provide a rationale for applying antioxidants during schizophrenic therapy. (C) 2009 Elsevier Ireland Ltd. All rights reserved.Ministry of Science Republic of Serbia [1430348, 143035B

Tianeptine's effects on spontaneous and Ca2+-induced uterine smooth muscle contraction

Tianeptine is a novel anti-depressant with an efficacy equivalent to that of classical anti-depressants. Additional beneficial effects include neuroprotection, anti-stress and anti-ulcer properties whose molecular mechanisms are still not completely understood but may involve changes in the anti-oxidant defence system. Herein, we have studied the effects of tianeptine on both contractile activity of isolated rat uteri and components of the endogenous anti-oxidative defence system. Tianeptine-induced dose-dependent inhibition of both spontaneous and Ca2+-induced contraction of uterine smooth muscle. The effect was more pronounced in the latter. Tianeptine treatment increased glutathione-peroxidase (GSH-Px) and catalase (CAT) activities in spontaneous and Ca2+-stimulated uteri. A significant decrease in glutathione-reductase (GR) activity in both spontaneous and Ca2+-induced uterine contractions after tianeptine treatment indicated a reduction in reduced glutathione and consequently a shift toward a more oxidised state in the treated uteri. In spontaneously contracting uteri, tianeptine caused a decrease in copper-zinc SOD (CuZnSOD) activity. Tianeptine's anti-depressant effects may be accomplished by triggering a cascade of cellular adaptations including inhibition of smooth muscle contractility and an adequate anti-oxidative protection response.Ministry of Science and Technological Development of the Republic of Serbia, University of Belgrade [173014

Lipid status, anti-oxidant enzyme defence and haemoglobin content in the blood of long-term clozapine-treated schizophrenic patients

Objective: Despite clozapine's unique effectiveness in patients with schizophrenia, a number of adverse effects have been recognised including abnormalities in lipid and glucose metabolisms. A high clozapine level in red blood cells (RBCs) and disturbed anti-oxidant enzyme activities in blood from schizophrenic patients prompted us to investigate lipid status and anti-oxidant enzyme defence in the blood of chronic schizophrenic patients on long-term clozapine therapy. Methods: Plasma lipids, RBC anti-oxidant enzyme activities and haemoglobin (Hb) content were measured using established procedures in a group of eighteen chronically-medicated (average 630 days of therapy) schizophrenic patients receiving clozapine (average dose of 295 mg/day) and data were compared with those from a group of eighteen well-matched normal controls. Results: Significantly higher levels of plasma triglycerides (by 47%, p<0.01) and total cholesterol and phospholipids (by 8% and 11%, respectively p<0.05) in patients were found. CuZn-superoxide dismutase (SOD1) activity was markedly higher (by 35%, p<0.001) while selenium-dependent glutathione peroxidase (GSH-Px1) activity was markedly lower (by 41%, p<0.001) in patients. In addition, metHb and HbA1c levels in patients were significantly higher (by 58% and 25%. respectively p<0.001). SOD1 activity was negatively correlated (p<0.001) to GSH-Px1 activity in patients. Conclusions:The findings support the view that ongoing oxidative stress may be a mechanism by which clozapine induces some adverse effects that increase the risk of diabetes and metabolic syndrome. If valid, this would indicate that in parallel with long-term clozapine treatment, schizophrenic patients could be encouraged to make some lifestyle changes to limit the detrimental effects of the medication. (C) 2009 Elsevier Inc. All rights reserved.Ministry of Science and Technological Development of the Republic of Serbia [142017, 143034