Oxidative stress biomarkers in treatment-responsive and treatment-resistant schizophrenia patients

Buosi, Patrick; Borghi, Fabio Aparecido; Lopes, A. M.; Facincani, Isabela; Fernandes-Ferreira, Rafael; Brancati, Camila Ive Ferreira Oliveira; Carmo, Tayanne Silva; Souza, Dorotéia Rossi Silva; Silva, Danilo; Almeida, Eduardo Alves de; Filho, Gerardo Araújo

doi:10.47626/2237-6089-2020-0078

Cited by 13 publications

(15 citation statements)

References 41 publications

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“…The fact that the patients are male, smokers, and have a disease duration of less than five years indicates differences in caspase-3 gene expression. Smoking that is related with oxidative stress in schizophrenia patients [37] may be an independent factor to induce caspase activation. Yu et al [38] showed that smoking increased cell apoptosis, causing an elevated cleaved-caspase 3/pro-caspase 3 ratio, and Bax expressesion but decreased Bcl-2 signals.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation Expression of the Caspase-3 and Caspase-9 Apoptotic Genes in Schizophrenia Patients

Dirican

Özcan

Uzunçakmak

et al. 2023

Clin Psychopharmacol Neurosci

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Objective: Apoptosis is programmed cell death that occurs by several pathways. Caspase-3 is induced by active caspase-9 via the intrinsic pathway. The aim of this research was to explore the expression of caspase-3 and caspase-9 in schizophrenia patients and healthy samples. Methods: RNA was isolated from the peripheral blood of 39 schizophrenia patients' and healthy samples. After cDNA synthesis, real time PCR (RT-PCR) was used to analyse caspase-3 and caspase-9 gene expression. The severity of psychopathological symptoms of schizophrenia was evaluated using the Positive and Negative Symptoms Scale for schizophrenia (PANSS) and Clinical Global Impressions (CGI). Results: The expression of caspase-3 and caspase-9 genes was higher in schizophrenia patients than in healthy samples (p = 0.012, p = 0.002, respectively). The increase in caspase-3 gene expression was significant with being male, smoking and with a duration of less than 6 years (p = 0.047, p = 0.049, p = 0.034, respectively). On the other hand, the increase in caspase-9 gene expression was significant in patients who is smoke, have children, and are under 33 years old (p = 0.040, p = 0.043, p = 0.045, respectively). A significant positive correlation was detected between the caspase-3 and caspase-9 gene expression (r = 0.3218, p = 0.049). Conclusion:Our findings indicate that caspase-3 and caspase-9 gene expression may activate cell death mechanisms by intrinsic apoptotic genes. Furthermore, caspase-3 and caspase-9 may play essential roles in different ways in schizophrenia. Hence there is a need to further study the apoptotic mechanism with expanded patient populations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation Expression of the Caspase-3 and Caspase-9 Apoptotic Genes in Schizophrenia Patients

Dirican

Özcan

Uzunçakmak

et al. 2023

Clin Psychopharmacol Neurosci

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“…35,36 GSTM1 null genotype might increase risk of SZ through brain inflammation induced by enzyme inactivity. [35][36][37]…”

Section: Discussionmentioning

confidence: 99%

“…GST genes were widely present in human body and were abundant in the kidney, liver, and lung. [36][37][38] In addition, GSTM1 and GSTP1 were detected in both human and rodent brains. 39 Notably, GSTM1 was also suggested that it is one of the most abundant proteins in astrocytes.…”

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confidence: 99%

Glutathione S-Transferase M1/T1 Polymorphisms and Schizophrenia Risk: A New Method for Quality Assessment and a Systematic Review

Liu¹,

Xu²,

Peng³

2023

NDT

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Background GST genes were reported to be involved in susceptibility to mental disorder. The results between deletions of GST genes and schizophrenia were inconclusive and confusing. Therefore, we performed this updated meta-analysis to outline the association using a new method for quality assessment. Methods Sixteen reported studies were selected, and the overall OR and 95% CI were calculated and analyzed by Review Manager 5.4 and STATE 12. The Newcastle-Ottawa Quality Assessment Scale (NOS) for case–control studies was rewritten to evaluate the quality of published studies, as there was no “Exposure” in these studies and other factors should be suggested to assess the quality. Results There was no significant association between deletions of GST genes and SZ risk ( p > 0.05 in Random model). We also failed to find a significant relation between null genotypes and SZ risk in East Asian population. Based on further analysis of PCR methods, GSTM1 null was weakly associated with SZ risk in 8 studies using multiplex PCR (OR = 1.17, 95% CI = 1.00–1.37, p = 0.05), but GSTT1 null was a protective factor for SZ risk (OR = 0.73, 95% CI = 0.56–0.94, p = 0.02). When stratified by rewritten NOS stars and deductions, GSTM1 null was significantly associated with SZ risk in 9 studies with high quality (OR = 1.24, 95% CI = 1.08–1.43, p = 0.002), and in 10 studies with no deductions (OR = 1.20, 95% CI = 1.05–1.38, p = 0.007). Conclusion GSTM1 null genotype may be a genetic risk factor for SZ in studies using multiplex PCR and high-quality studies. However, GSTT1 null might be a protective factor. Besides, we provided a new method for quality assessment and it was useful and should be promoted in further analysis.

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“…Its annual prevalence was as high as 0.6% ( 1 ), which has a far-reaching impact on personal life and society, and it is easy to lead to lifelong disability. At present, the treatment of SCZ is still mainly drug treatment, its curative effect is limited, and adverse drug reactions are difficult to avoid, although it does not make the antipsychotics not being tolerable in most cases ( 2 ). Additionally, it has been suggested that identifying different discontinuation patterns for antipsychotics may contribute to optimize treatment selection in SCZ ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Paeoniflorin Rescued MK-801-Induced Schizophrenia–Like Behaviors in Mice via Oxidative Stress Pathway

2022

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Schizophrenia (SCZ) affects approximately 1% population worldwide, and the first-line antipsychotics have partial reactivity or non-reactivity with side effects. Therefore, there is an urgent need to find more effective drugs. Paeoniflorin (PF) is the main effective component of traditional Chinese medicine from white peony, red peony and peony bark, which acts as a neuroprotective agent. The purpose of this study was to investigate whether PF can rescue MK-801 induced schizophrenia-like behavior in mice. Our results demonstrated that intragastric administration of PF ameliorated MK-801 induced schizophrenia–like behaviors in mice as demonstrated by prepulse inhibition of acoustic startle response, fear conditioning test for memory and open field test for activity. In contrast, the first-line antipsychotics-olanzapine reversed the prepulse inhibition deficits and hyperactivities, but not memory deficits, in the model mice. Further analysis showed that PF reduced oxidative stress in the MK-801-treated mice, as evidenced by the increased superoxide dismutase levels and decreased malondialdehyde levels in the blood of the model mice. In addition, PF treatment inhibited the expression of the apoptotic protein Bax and restored the expression of tyrosine hydroxylase in the brains of the model mice. in vitro data indicated that PF protected against oxidative stress induced neurotoxicity in the primary cultured hippocampal neurons. In conclusion, our results were the first to provide evidence that PF rescued schizophrenia-like behaviors (both positive symptoms and cognitive impairments) in rodents through oxidative stress pathway, and therefore provide a novel strategy for treatment of SCZ. However, more pre-clinical and clinical research are needed to translate the present findings into clinics for a treatment of schizophrenia.

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Oxidative stress biomarkers in treatment-responsive and treatment-resistant schizophrenia patients

Cited by 13 publications

References 41 publications

Evaluation Expression of the Caspase-3 and Caspase-9 Apoptotic Genes in Schizophrenia Patients

Evaluation Expression of the Caspase-3 and Caspase-9 Apoptotic Genes in Schizophrenia Patients

Glutathione S-Transferase M1/T1 Polymorphisms and Schizophrenia Risk: A New Method for Quality Assessment and a Systematic Review

Paeoniflorin Rescued MK-801-Induced Schizophrenia–Like Behaviors in Mice via Oxidative Stress Pathway

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