Abdelhamid Kerkeni

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.

In depth analysis of the in vivo toxicity of nanoparticles of porous iron(III) metal–organic frameworks

In vivo acute toxicity of high doses of nanoparticles of three different porous iron(III) carboxylate Metal–Organic Frameworks (nanoMOFs) was intravenously investigated in rats by evaluating their distribution, metabolism and excretion. All studied parameters (serum, enzymatic, histological, etc.) are in agreement with a low acute toxicity. The mechanism of degradation and excretion of the nanoMOFs has been evidenced and shows that the nanoparticles are rapidly sequestered by the liver and spleen, then further biodegraded and directly eliminated in urine or feces without metabolization and substantial toxicity.

The prolongation of the lifespan of rats by repeated oral administration of [60]fullerene.

Countless studies showed that [60]fullerene (C(60)) and derivatives could have many potential biomedical applications. However, while several independent research groups showed that C(60) has no acute or sub-acute toxicity in various experimental models, more than 25 years after its discovery the in vivo fate and the chronic effects of this fullerene remain unknown. If the potential of C(60) and derivatives in the biomedical field have to be fulfilled these issues must be addressed. Here we show that oral administration of C(60) dissolved in olive oil (0.8 mg/ml) at reiterated doses (1.7 mg/kg of body weight) to rats not only does not entail chronic toxicity but it almost doubles their lifespan. The effects of C(60)-olive oil solutions in an experimental model of CCl(4) intoxication in rat strongly suggest that the effect on lifespan is mainly due to the attenuation of age-associated increases in oxidative stress. Pharmacokinetic studies show that dissolved C(60) is absorbed by the gastro-intestinal tract and eliminated in a few tens of hours. These results of importance in the fields of medicine and toxicology should open the way for the many possible -and waited for- biomedical applications of C(60) including cancer therapy, neurodegenerative disorders, and ageing.

Peripheral Blood Markers of Oxidative Stress in Parkinson’s Disease

Oxidative stress and generation of reactive oxygen species are believed to be implicated in Parkinson’s disease (PD). Erythrocyte activity of superoxide dismutase (SOD) and catalase, the blood glutathione system, and plasma levels of thiobarbituric-acid-reactive substances (TBARS) were measured in 80 PD patients. These biochemical parameters were also measured in 29 age-matched controls. Patients with PD had significantly higher red blood corpuscle (RBC) activity of SOD. The mean RBC activity of catalase in PD patients did not differ significantly from those of controls. RBC catalase activity was significantly lower in advanced cases of PD compared to early cases. Oxidized glutathione was significantly higher in RBCs of PD patients, although there were no changes in total glutathione and reduced glutathione compared to controls. TBARS content was increased in patients with PD. Levodopa therapy, age and duration of illness did not significantly influence the measured parameters. Our study supports the previous hypothesis that oxidative stress is implicated in the pathogenesis of PD. Perspectives for treatment of PD in the future could include antioxidant therapy.

Influence of combined treatment with zinc and selenium on cadmium induced testicular pathophysiology in rat

The present study was conducted to evaluate the potential benefit of combined treatment with zinc (Zn) and selenium (Se) in reversing cadmium (Cd)-induced testicular pathophysiology compared to Se or Zn treatment alone in rats. For this purpose, male rats received either tap water, Cd, Cd+Zn, Cd+Se or Cd+Zn+Se in their drinking water, for 35 days. Cd exposure caused a significant decrease in plasma and testicular concentrations of Se and Zn which was accompanied by decreased plasma testosterone level, sperm count and motility, enzymatic activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) as well as by increased lipid peroxidation (as malondialdehyde, MDA). With Se or Zn administration, during exposure to Cd, only partial corrective effects on depletion of testicular and plasma Se and Zn levels, sperm characteristics and oxidative stress have been observed. The combined treatment of Cd-exposed animals with Se and Zn assured a more significant decrease in plasma and testicular Cd concentrations and a more efficient protection against the observed testicular damage as evidenced by the total prevention of both Se and Zn deprivation and by the entire restoration of the sperm motility and the testicular antioxidant status.

Reversal of cadmium-induced oxidative stress in rat erythrocytes by selenium, zinc or their combination

The aim of this study was to evaluate the potential benefit of combined treatment with zinc (Zn) and selenium (Se) in reversing cadmium (Cd)-induced oxidative stress in erythrocytes, compared to Se or Zn treatment alone in rats exposed to Cd. For this purpose, 30 adult male Wistar albino rats were equally divided into control and four treated groups received either 200ppm Cd (as CdCl(2)), 200ppm Cd+500ppm Zn (as ZnCl(2)), 200ppm Cd+0.1ppm Se (as Na(2)SeO(3)), or 200ppm Cd+500ppm Zn+0.1ppm Se in their drinking water for 35 days. Marked alterations of antioxidative system were found in Cd-treated rats. Activities of catalase (CAT) and glutathione peroxidise (GSH-Px) as well as the total glutathione (GSH) contents in erythrocytes were significantly decreased, whereas the activity of total superoxide dismutase (SOD) was significantly increased. The treatment of Cd-exposed rats with Se alone had no significant effect on the Cd-induced increase in the SOD activity but increased significantly the CAT and GSH-Px activities and partially reversed Cd-induced depletion of GSH levels in erythrocytes. The treatment of Cd-exposed animals with Zn alone partially reversed Cd-induced increase in SOD activity and Cd-induced decrease in GSH-Px activity. The combined treatment of Cd-exposed animals with Se and Zn was more effective than that with either of them alone in reversing Cd-induced decrease in CAT and GSH-Px activities and Cd-induced increase in SOD activity. This treatment also partially restored Cd-induced depletion of GSH. These results could be important for the further development of better treatments for people and/or animals exposed to Cd.

Cadmium bioaccumulation in three benthic fish species, Salaria basilisca, Zosterisessor ophiocephalus and Solea vulgaris collected from the Gulf of Gabes in Tunisia

To select a marine teleost fish which can be used as a bioindicator of cadmium (Cd) pollution in the Gulf of Gabes in Tunisia, Cd concentrations in liver and gill were compared in three benthic fish species including Salaria basilisca, Zosterisessor ophiocephalus and Solea vulgaris. Fish samples were collected from three selected sites in the Gulf of Gabes, with different degrees of Cd contamination: the industrialized coast of Sfax (S1), the coast of Douar Chatt (S2) and the coast of Luza (S3). The results shows that Cd concentrations in both sediment and water collected from S1 were significantly higher (p < 0.0001) than those from S2 and S3. For each species, Cd concentrations, in both liver and gill, showed the decreasing order: S1 > S2 > S3. The highest concentration of Cd was detected in the liver of S. basilisca, and only S. basilisca showed bioaccumulation factors (BAF) greater than 1 in all studied sites. In S1 and S2, BAF values respect the following order: S. basilisca > Z. ophiocephalus > S. vulgaris. These results of significant bioaccumulation of Cd, in terms of hepatic concentrations and bioaccumulation factors, indicated that S. basilisca can be used as bioindicator to evaluate the evolution of Cd pollution in the Gulf of Gabes.

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.