Monia Raffa

Decreased glutathione levels and antioxidant enzyme activities in untreated and treated schizophrenic patients

There is substantial evidence found in the literature that supports the fact that the presence of oxidative stress may play an important role in the physiopathology of schizophrenia. Previous studies have reported the occurrence of impairments in the glutathione levels and the activities of the antioxidant enzymes in patients suffering from schizophrenia. However, most of these studies were performed on treated patients. The present study evaluated treated schizophrenic patients (n=52) along with neuroleptic-free or untreated schizophrenic patients (n=36) and healthy controls (n=46). The blood glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr), and oxidized glutathione (GSSG) as well as the activities of the antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were measured. The psychopathology of the patients was assessed through the Clinical Global Impressions-severity (CGI-severity). The tests revealed that in comparison with the healthy controls, the schizophrenic patients showed significantly lower levels of GSHr, SOD, and CAT. Among the schizophrenic patients, the activities of the antioxidant enzymes SOD and CAT were recorded to be significantly lower in untreated patients than in the treated ones. In addition, the levels of both GSHt and GSHr were found to be inversely correlated with the obtained CGI-severity score. These results evidently suggest that a decrease in the glutathione levels and the activities of the antioxidant enzymes in patients diagnosed with schizophrenia is not related to neuroleptic treatment and could be considered as a biological indicator of the degree of severity of the symptoms of schizophrenia.

Decreased glutathione levels and impaired antioxidant enzyme activities in drug-naive first-episode schizophrenic patients

BackgroundThe aim of this study was to determine glutathione levels and antioxidant enzyme activities in the drug-naive first-episode patients with schizophrenia in comparison with healthy control subjects.MethodsIt was a case-controlled study carried on twenty-three patients (20 men and 3 women, mean age = 29.3 ± 7.5 years) recruited in their first-episode of schizophrenia and 40 healthy control subjects (36 men and 9 women, mean age = 29.6 ± 6.2 years). In patients, the blood samples were obtained prior to the initiation of neuroleptic treatments. Glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr) and oxidized glutathione (GSSG) and antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were determined by spectrophotometry.ResultsGSHt and reduced GSHr were significantly lower in patients than in controls, whereas GSSG was significantly higher in patients. GPx activity was significantly higher in patients compared to control subjects. CAT activity was significantly lower in patients, whereas the SOD activity was comparable to that of controls.ConclusionThis is a report of decreased plasma levels of GSHt and GSHr, and impaired antioxidant enzyme activities in drug-naive first-episode patients with schizophrenia. The GSH deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in schizophrenia early in the course of illness. Finally, our results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies for schizophrenia from early stages.

Reduced antioxidant defense systems in schizophrenia and bipolar I disorder

Numerous evidence and proofs suggest that the oxidative stress contributes to the pathogenesis of schizophrenia (SZ) and bipolar disorder (BD). The aim of this study is to determine the glutathione levels and the antioxidant enzyme activities in blood samples of patients suffering from SZ and patients with bipolar disorder in comparison with the healthy controlled subjects. It was a case-controlled study carried on upon three groups: forty-six SZ patients (41 men and 5 women, mean age=33.2±7years), thirty BD patients (25 men and 5 women, mean age=31.3±8years) and forty healthy controls (33 men and 7 women, mean age=32.3±7years). The glutathione levels are the total glutathione (GSHt), the reduced glutathione (GSHr), and the oxidized glutathione (GSSG) and the antioxidant enzyme activities that are the superoxide dismutase (SOD), the glutathione peroxidase (GPx), and the catalase (CAT) are determined by the spectrophotometer. We noticed that the GSHt and the GSHr levels significantly decreased in both SZ and BD patients in comparison with the healthy control subjects. As for SOD and CAT activities they remained lower for the patients with SZ when compared both with the controls or the BD patients. We noticed as well that the CAT activity was significantly lower in the BD group than that in the control group, whereas, GPx activity showed no significant change in each group. Hence, this report of the decreased plasma levels of GSHt and GSHr, and the impaired antioxidant enzyme activities in SZ and BD patients aims at highlighting the GSH deficit that seems to be contributing to these disorders, and showing that it may be an important indirect biomarker of the oxidative stress for the SZ and BD.

Impact of seminal trace element and glutathione levels on semen quality of Tunisian infertile men

BackgroundGrowing evidence indicates that oxidative stress can be a primary cause of male infertility. Non-enzymatic antioxidants play an important protective role against oxidative damages and lipid peroxidation. Human seminal plasma is a natural reservoir of antioxidants. The aim of this study was to determine glutathione (GSH) concentrations, trace element levels (zinc and selenium) and the lipid peroxidation end product, malondialdehyde (MDA), in the seminal plasma of men with different fertility potentials.MethodsSemen samples from 60 fertile men (normozoospermics) and 190 infertile patients (74 asthenozoospermics, 56 oligozoospermics, and 60 teratozoospermics) were analyzed for physical and biochemical parameters. Zinc (Zn) and selenium (Se) levels were estimated by atomic absorption spectrophotometry. Total GSH (GSHt), oxidized GSH (GSSG), reduced GSH (GSHr) and MDA concentrations were measured spectrophotometrically.ResultsZn and Se concentrations in seminal plasma of normozoospermics were more elevated than the three abnormal groups. Nevertheless, only the Zn showed significant differences. On the other hand, Zn showed positive and significant correlations with sperm motility (P = 0.03, r = 0.29) and count (P < 0.01, r = 0.49); however Se was significantly correlated only with sperm motility (P < 0.01, r = 0.36). GSHt, GSSG and GSHr were significantly higher in normozoospermics than in abnormal groups. We noted a significant association between seminal GSHt and sperm motility (P = 0.03). GSSG was highly correlated to sperm motility (P < 0.001) and negatively associated to abnormal morphology (P < 0.001). GSHr was significantly associated to total sperm motility (P < 0.001) and sperm count (P = 0.01). MDA levels were significantly higher in the three abnormal groups than in normozoospermics. Rates of seminal MDA were negatively associated to sperm motility (P < 0.01; r = -0.24) and sperm concentration (P = 0.003; r = -0.35) Meanwhile, there is a positive correlation between seminal lipid peroxidation and the percentage of abnormal morphology (P = 0.008).ConclusionsThis report revealed that decreased seminal GSH and trace element deficiencies are implicated in low sperm quality and may be an important indirect biomarker of idiopathic male infertility. Our results sustain that the evaluation of seminal antioxidant status in infertile men is necessary and can be helpful in fertility assessment from early stages.

Relationship between GSTM1 and GSTT1 polymorphisms and schizophrenia: a case-control study in a Tunisian population.

There is substantial evidence found in the literature that supports the fact that the presence of oxidative stress may play an important role in the pathophysiology of schizophrenia. The glutathione S-transferases (GSTs) forms one of the major detoxifying groups of enzymes responsible for eliminating products of oxidative stress. Interindividual differences observed in the metabolism of xenobiotics have been attributed to the genetic polymorphism of genes coding for enzymes involved in detoxification. Thus, in this study we investigated the association of glutathione S-transferase Mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) gene deletion polymorphisms and schizophrenia in a Tunisian population. A case-control study including 138 schizophrenic patients and 123 healthy controls was enrolled. The GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). No association was found between the GSTM1 genotype and schizophrenia, whereas the prevalence of the GSTT1 active genotype was significantly higher in the schizophrenic patients (57.2%) than in the controls (45.5%) with (OR=0.6, IC 0.37-0.99, p=0.039). Thus, we noted a significant association between schizophrenia and GSTT1 active genotype. Furthermore, the combination of the GSTM1 and GSTT1 null genotypes showed a non-significant trend to an increased risk of schizophrenia. The present finding indicated that GSTT1 seems to be a candidate gene for susceptibility to schizophrenia in at least Tunisian population.

2699 – Glutathione levels in patients with chronic and fist-episode schizophrenia and association with neurological soft signs

Introduction Recent studies have suggested that the deficit of glutathione (GSH), a major antioxidant, seems to play a role in the pathophysiology of schizophrenia. Moreover, oxidative stress may contribute to the development of neurological abnormalities, including tardive dyskinesia and parkinsonism symptoms. Objectives To determine plasma glutathione levels and to explore their association with neurological soft signs (NSS) in patients with chronic and first-episode schizophrenia. Methods A case-control study carried-out on three groups: sixty clinically stable patients with chronic schizophrenia, twentythree patients with first-episode schizophrenia and thirty matched healthy controls. Glutathione levels: total (GSHt), reduced (GSHr) and oxidized glutathione (GSSG) were determined by spectrophotometry. NSS were assessed in three groups by a standardized neurological examination (Krebs et al., 2000). Results Plasmatic GSHt and GSHr levels were significantly decreased in patients with chronic and first-episode schizophrenia. All NSS scores were significantly higher in two groups of patients compared to controls. No association was found between NSS scores and glutathione levels in patients with chronic schizophrenia. However, in patients with firstepisode, a negative correlation was found between GSHt levels and involuntary movement sub-score (r= -0.62, p=0.008). Conclusion These results suggest that GSH deficit is not related to the stage of disease and may be an important indirect biomarker of oxidative stress in schizophrenia. The association between low GSHt level as a marker of oxidative stress and involuntary movements could suggest that oxidative stress may contribute to the brain damage which leads to an increased prevalence of these NSS.

2700 – Glutathione levels and schizotypy scores in unaffected first-degree relatives of patients with schizophrenia

Introduction Several studies have shown a glutathione (GSH) deficit in patients with schizophrenia. It may in part arise from a genetically compromised synthesis of GSH, the major cellular antioxidant and redox-regulator. First-degree relatives of patients with schizophrenia share many susceptibility genes of this disease. Objectives The objectives of this study were to determine plasma glutathione levels in patients with schizophrenia and their unaffected first-degree relatives of compared to healthy controls and to examine the correlation between glutathione levels and schizotypy scores in unaffected relatives. Methods We included 60 patients with schizophrenia, 33 of their unaffected siblings and 30 healthy controls with no family psychiatric history. The blood glutathione levels: total (GSHt), reduced (GSHr), and oxidized glutathione (GSSG) were measured by spectrophotometry. Schizotypy scores were assessed by the schizotypal personality questionnaire (SPQ). Results GSHt and GSHr were significantly lower in patients than in controls, whereas there was no difference in glutathione levels between unaffected relatives and healthy controls. Moreover, no correlation was found between glutathione levels and schizotypy scores in unaffected relatives of patients with schizophrenia. Conclusions These results reveal that unaffected relatives of patients with schizophrenia didn’t have a GSH deficit. In the same group, no correlation was found between glutathione levels and schizotypy scores which considered a vulnerability marker for schizophrenia. These findings disagree with our hypothesis that GSH deficit could be a biological marker of vulnerability to schizophrenia. However, further studies are necessary to explore this hypothesis.