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

Raffa, Monia; Mechri, A.; Othman, Leila Ben; Fendri, C.; Gaha, L.; Kerkeni, Abdelhamid

doi:10.1016/j.pnpbp.2009.06.018

Cited by 154 publications

(109 citation statements)

References 30 publications

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“…Gluthatione reductase activity, essential to maintain the reducing capability of the cell, was found to be significantly increased in SCZ patients compared to normal controls [46], contradicting previous studies [57,58]. Hence, these results are in line with an existing dysregulation of the oxidant-antioxidant balance in the pathophisiology of SCZ.…”

Section: Oxidative Stress-a Field For New Tailored Therapies?contrasting

confidence: 71%

“…Although the this confirms some studies [57,58], it also contradicts others that found no difference in SOD activity between chronic SCZ patients and healthy controls [59] or found increased SOD activity in FEP and chronic SCZ patients compared to normal controls [60]. As in the latter study, the levels of SOD were greater in FEP than in chronic patients, the authors suggested that OS might occur in the initial phase of SCZ, getting worse with the chronicity of the disorder.…”

Section: Oxidative Stress-a Field For New Tailored Therapies?supporting

confidence: 70%

“…When compared to healthy controls, gluthatione peroxidase was found to be decreased and catalase increased in SCZ [46]. Nevertheless, some previous studies reported the opposite [57,58].…”

Section: Oxidative Stress-a Field For New Tailored Therapies?mentioning

confidence: 59%

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Biomarkers and schizophrenia: a qualitative review

Silva¹,

Pinto²

2017

IJCNMH

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Schizophrenia (SCZ) is a psychiatric disorder with a broad spectrum of biological and clinical manifestations of yet not completely clear pathophysiological mechanisms. Several lines of evidence have been supporting the idea that immunoinflammatory, oxidative, hormonal and cellular dysfunctions are implicated on the biomolecular basis of SCZ. However, accurate diagnosis and selection of appropriate treatments remains challenging as a result of the scarcity of objective tests. Furthermore, there is a compelling need to find biomarkers that could predict drug response and tailor pharmacological treatment, particularly in drug-naïve first episode psychosis (FEP). Hence, numerous technologies have been employed in order to search for SCZ biological markers, but evidence relating them to treatment efficacy is lacking. In this regard, some preliminary data suggest promising results. The current review provides information on: (1) potential biomarkers associated with biological disturbances and (2) biological markers associated with treatment response.

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Section: Oxidative Stress-a Field For New Tailored Therapies?contrasting

confidence: 71%

Section: Oxidative Stress-a Field For New Tailored Therapies?supporting

confidence: 70%

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Biomarkers and schizophrenia: a qualitative review

Silva¹,

Pinto²

2017

IJCNMH

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“…Studies performed in schizophrenia patients have generally suggested a compromised antioxidant system, but this is not always consistent with specific observed parameters, which on the whole, show evidences of dysregulation. Reduced levels of the antioxidant enzymes are generally reported in patients with schizophrenia compared with controls [30][31][32][33]. However, some studies have advocated a strengthening of antioxidant status in schizophrenia [34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Increased Oxidant Stress and Inflammation in Patients with Chronic Schizophrenia

Yeğin¹,

Ay²,

Aydın³

et al. 2012

IJCM

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Background: Several lines of evidence, including postmortem studies, suggest increased oxidative stress and inflammation in patients with schizophrenia. Alteration of oxidative stress markers has been reported in schizoprenia studies, but with inconsistent results. Oxidized low-density lipoproteins (oxLDL) have been reported to be capable of eliciting neurocytotoxicity. On the other hand, paraoxonase (PON1), an arylesterase(ARE), plays a role in protection against oxidative modifications of LDL and is considered to be one of the antioxidant enzymes. There are no studies showing the changes in oxidative stress and inflammation together, nor the activities of PON1 and ARE in schizophrenic patients. In this study, we examined PON1, ARE activities and oxidative/anti-oxidative markers in patients with chronic schizophrenia and healthy controls. Methods: We recruited 30 male chronic schizophrenic patients and 30 male healthy control subjects and examined C-reactive protein(CRP), fibrinogen, PON1, ARE and plasma total antioxidant status (TAS) and total oxidant status (TOS), oxidative stress index(OSI) in both groups. Schizophrenia symptoms were assessed using the positive and negative syndrome scale (PANSS). The related routine lipid profile parameters including HDL were also examined. Results: Patients had significantly higher CRP, fibrinogen, TOS and OSI levels; but the patients and control subjects did not differ on activities of the antioxidant enzymes PON1 and ARE. Interestingly, there were not any group differences in the lipid profile parameters except the triglyceride levels, that increased significantly in the patient group. Conclusions: In the present study, reporting the ARE activities besides the PON1 activities in schizophrenic patients for the first time, we showed that PON1 and ARE enzyme activities were not statistically different in patients with chronic schizophrenia. This study provides additional evidence of increased oxidative stress and inflammation in chronic schizophrenia, but no alterations in the antioxidant status were observed. Our results suggest that other mechanisms than the high density lipoprotein(HDL)-disfunctionality, namely decreases in PON1 or ARE enzyme activities, are more important in oxidative or antioxidative pathophysiological processes in schizophrenia.

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“…In addition, S-glutathionylation regulates many proteins involved in endoplasmic reticulum (ER) stress and the unfolded protein response that accompanies oxidative stress (Townsend, 2007). A number of neurodegenerative diseases and psychiatric disorders have been linked to abnormal GSH levels, ER stress, and accompanying S-glutathionylation of proteins, such as Parkinson's disease (Chinta et al, 2006;Sian et al, 1994), Alzheimer's disease (Di Domenico et al, 2009;Zhu et al, 2006), Huntington's disease (Klepac et al, 2007), and schizophrenia (Radonjic et al, 2010;Raffa et al, 2009;Steullet et al, 2006). GSH cannot cross cell membranes and therefore needs to be synthesized de novo.…”

Section: Introductionmentioning

confidence: 99%

Cocaine-Induced Adaptations in Cellular Redox Balance Contributes to Enduring Behavioral Plasticity

Uys

Knackstedt

Hurt

et al. 2011

Neuropsychopharmacol

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Impaired glutamate homeostasis in the nucleus accumbens has been linked to cocaine relapse in animal models, and results in part from cocaine-induced downregulation of the cystine-glutamate exchanger. In addition to regulating extracellular glutamate, the uptake of cystine by the exchanger is a rate-limiting step in the synthesis of glutathione (GSH). GSH is critical for balancing cellular redox in response to oxidative stress. Cocaine administration induces oxidative stress, and we first determined if downregulated cystineglutamate exchange alters redox homeostasis in rats withdrawn from daily cocaine injections and then challenged with acute cocaine. Among the daily cocaine-induced changes in redox homeostasis were an increase in protein S-glutathionylation and a decrease in expression of GSH-S-transferase pi (GSTpi). To mimic reduced GSTpi, a genetic mouse model of GSTpi deletion or pharmacological inhibition of GSTpi by administering ketoprofen during daily cocaine administration was used. The capacity of cocaine to induce conditioned place preference or locomotor sensitization was augmented, indicating that reducing GSTpi may contribute to cocaineinduced behavioral neuroplasticity. Conversely, an acute cocaine challenge after withdrawal from daily cocaine elicited a marked increase in accumbens GSTpi, and the expression of behavioral sensitization to a cocaine challenge injection was inhibited by ketoprofen pretreatment; supporting a protective effect by the acute cocaine-induced rise in GSTpi. Together, these data indicate that cocaineinduced oxidative stress induces changes in GSTpi that contribute to cocaine-induced behavioral plasticity.

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

Cited by 154 publications

References 30 publications

Biomarkers and schizophrenia: a qualitative review

Biomarkers and schizophrenia: a qualitative review

Increased Oxidant Stress and Inflammation in Patients with Chronic Schizophrenia

Cocaine-Induced Adaptations in Cellular Redox Balance Contributes to Enduring Behavioral Plasticity

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