Evolution of inflammatory dysregulation and oxidative stress in patients with first episode of mania

IntroductionRecent studies have focused on the imbalance in inflammatory and antioxidant pathways as possible causes of the underlying neurodegenerative processes in bipolar disorder. Thus, the study of these pathways in first episodes of mania (FEM) can increase knowledge about this issue.AimTo compare plasma concentrations of pro-inflammatory (MCP-1, PGE2, TNFα) and oxidative parameters (TAS, NO2 and TBARS) between controls and FEM patients and to analyze the evolution of these parameters in patients from baseline to 6 months assessment time.MethodsThis study included 44 FEM patients and 79 healthy controls, aged 18 to 40. Blood samples were available for controls at baseline and for patients at baseline and 6 months after. TAS and TBARS were measured using non-EIA assay kits, N02 was measured with Griess method and PGE2, MCP-1 and TNFα with ELISA kits.ResultsAt baseline, TAS was significantly lower in patients than in controls and TBARS, MCP-1 and TNFα were significantly higher in patients. Among patients, TAS and MCP1 were lower at 6 months than at the illness onset and PGE2 and NO2 were significantly higher than at baseline.ConclusionPatients presented an increased oxidative damage and also a higher activation of pro-inflammatory pathways than healthy controls at baseline. After 6 months their level of oxidative stress continue increased. Pro-inflammatory parameters decreased overtime (MCP-1 and TNF α) but PGE2, increased surprisingly. This can be due to the fact that antipsychotics are not able to completely reverse baseline inflammation.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Sex Difference in the Interrelationship Between TNF-α and Oxidative Stress Status in First-episode Drug-naïve Schizophrenia

10.21203/rs.3.rs-126760/v1 ◽

2020 ◽

Author(s):

Minghuan Zhu ◽

Zhenjing Liu ◽

Jaelin Rippe ◽

Mst. Sadia Sultana ◽

Kang Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Sex Differences ◽

Sex Difference ◽

Psychotic Symptoms ◽

First Episode ◽

Healthy Controls ◽

Tnf Α ◽

Drug Naïve ◽

Male Patients ◽

And Oxidative Stress

Abstract BackgroundIncreasing evidence indicates that dysregulated TNF-α and oxidative stress (OxS) contribute to the pathophysiology of schizophrenia. Additionally, previous evidence has demonstrated sex differences in many aspects of schizophrenia including clinical characteristics, cytokines and OxS markers. However, to the best of our knowledge, there is no study investigating sex differences in the association between TNF-α, the OxS system, and their interaction with clinical symptoms in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients. MethodsA total of 119 FEDN schizophrenia patients and 135 healthy controls were recruited for this study. Serum TNF-α, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were measured. The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate psychotic symptoms. Two-way ANOVA, partial correlation analysis and multivariate regression analysis were performed. ResultsA sex difference in MDA levels was demonstrated only in healthy controls (F = 7.06, p Bonferroni = 0.045) and not seen in patients. Furthermore, only male patients had higher MDA levels than male controls (F = 8.19, p Bonferroni = 0.03). Additionally, sex differences were observed in the association of TNF-α and MDA levels with psychotic symptoms (all pBonferroni<0.05). The interaction of TNF-α and MDA was only associated with general psychopathology symptom in male patients (B = -0.07, p = 0.02). ConclusionOur results demonstrate the sex difference in the relationship between TNF-α, MDA, and their interaction with psychopathological symptoms of patients with schizophrenia.

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Sex difference in the interrelationship between TNF-α and oxidative stress status in first-episode drug-naïve schizophrenia

Journal of Neuroinflammation ◽

10.1186/s12974-021-02261-5 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Minghuan Zhu ◽

Zhenjing Liu ◽

Yanhong Guo ◽

Mst. Sadia Sultana ◽

Kang Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Sex Differences ◽

Sex Difference ◽

Psychotic Symptoms ◽

First Episode ◽

Healthy Controls ◽

Tnf Α ◽

Drug Naïve ◽

Male Patients ◽

And Oxidative Stress

Abstract Background Increasing evidence indicates that dysregulated TNF-α and oxidative stress (OxS) contribute to the pathophysiology of schizophrenia. Additionally, previous evidence has demonstrated sex differences in many aspects of schizophrenia including clinical characteristics, cytokines, and OxS markers. However, to the best of our knowledge, there is no study investigating sex differences in the association between TNF-α, the OxS system, and their interaction with clinical symptoms in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients. Methods A total of 119 FEDN schizophrenia patients and 135 healthy controls were recruited for this study. Serum TNF-α, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were measured. The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate psychotic symptoms. Two-way ANOVA, partial correlation analysis, and multivariate regression analysis were performed. Results A sex difference in MDA levels was demonstrated only in healthy controls (F = 7.06, pBonferroni = 0.045) and not seen in patients. Furthermore, only male patients had higher MDA levels than male controls (F = 8.19, pBonferroni = 0.03). Additionally, sex differences were observed in the association of TNF-α and MDA levels with psychotic symptoms (all pBonferroni < 0.05). The interaction of TNF-α and MDA was only associated with general psychopathology symptom in male patients (B = − 0.07, p = 0.02). Conclusion Our results demonstrate the sex difference in the relationship between TNF-α, MDA, and their interaction with psychopathological symptoms of patients with schizophrenia.

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First bipolar episode and functionality: Relation with depressive symptoms and inflammation levels

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.154 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S122-S123 ◽

Cited By ~ 1

Author(s):

M. Martinez-cengotitabengoa ◽

C. Bermudez-ampudia ◽

M.P. Lopez ◽

A. Garcia-alocen ◽

I. Gonzalez-ortega ◽

...

Keyword(s):

Oxidative Stress ◽

Depressive Symptoms ◽

Manic Episode ◽

Inflammatory Factors ◽

First Episode ◽

Illness Onset ◽

Inflammatory Parameters ◽

General Functioning ◽

Competing Interest ◽

One Year

IntroductionIt is important to make an early and effective intervention from the first bipolar episode. The presence of depressive symptoms in the course of a manic episode could influence negatively the evolution and the prognosis of the patient. Inflammation and oxidative stress are also related with functionality.ObjectivesTo explore the relationship between depressive symptoms during a first episode of mania, inflammatory parameters and patient functionality during the follow-up.MethodWe included in the study 92 are patients with a first manic episode and 92 matched healthy controls. We compared 13 inflammatory/oxidative stress parameters measured at baseline (TFNα, IL6, PGE2, MCP1, TBARS, NO2, SOD, CAT, GSHTOT, GSSG, GSHfree, GPx, TAS) between both groups. Between patients, 46 presented pure mania (PM) (no depressive symptoms) and 46 mixed mania (MM) (with depressive symptoms). We explored the influence of inflammatory factors in functionality, exploring differences between PM and MM. To measure patients’ general functioning one year after illness onset, we used the Functional Assessment Short Test (FAST).ResultsWe found significant differences in TFNα, MCP1 and TBARS (higher in patients) and in SOD, GSHtot, GSSG, GSHfree, GPx and TAS levels (lower in patients). Only In MM group, there was a significant influence of SOD and GSHfree in FAST scores suggesting that a higher antioxidant levels at baseline the patient functionality improves one year after.ConclusionsSome parameters of oxidative stress at baseline are related with patient's functionality one year after the first episode of mania, but only when mania debuts with depressive symptons simultaneously.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Insulin Resistance and Oxidative Stress: In Relation to Cognitive Function and Psychopathology in Drug-Naïve, First-Episode Drug-Free Schizophrenia

Frontiers in Psychiatry ◽

10.3389/fpsyt.2020.537280 ◽

2020 ◽

Vol 11 ◽

Author(s):

Qi Tao ◽

Yu Miao ◽

Huihui Li ◽

Xiuxia Yuan ◽

Xufeng Huang ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Cognitive Function ◽

Serum Levels ◽

First Episode ◽

Healthy Controls ◽

Healthy Control ◽

Drug Naïve ◽

Drug Free ◽

And Oxidative Stress

Objective: The present study aimed to examine whether insulin resistance and oxidative stress are associated with cognitive impairment in first-episode drug-free schizophrenia (SZ) patients.Methods: Ninety first-episode SZ patients and 70 healthy controls were enrolled. Fasting insulin (FINS) and markers of oxidative stress [oxidized glutathione (GSSG), superoxide dismutase (SOD), nitric oxide (NO) and uric acid (UA) levels] were measured in serum before pharmacological treatment was initiated. Psychiatric symptoms and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB), respectively. In addition, the homeostatic model assessment of insulin resistance (HOMA-IR) was also studied.Results: HOMA-IR and serum levels of GSSG and NO were significantly higher in SZ patients than in healthy controls (P < 0.001), while the serum levels of SOD were significantly lower than in healthy controls (P < 0.001). HOMA-IR, GSSG and NO levels were significantly correlated to the total cognitive function scores of the patient group (r = −0.345,−0.369,−0.444, respectively, P < 0.05). But these factors were not co-related to the cognitive functions in the healthy control group. And, levels of SOD, UA were not associated with the total cognitive function scores in both the patient and the healthy control groups. NO was positively correlated with general pathological and the total score in the PANSS, and was negatively correlated with six cognitive domains (r = −0.316 to −0.553, P < 0.05).Conclusions: The levels of insulin resistance and oxidative stress are elevated, and correlated with the severity of cognitive impairment in drug-naïve, first-episode SZ patients. Treatment approaches targeting on reducing insulin resistance and oxidative stress may improve cognitive function in SZ patients.

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Endothelial Activation and Oxidative Stress in Neurovascular Defects of the Retina

Current Pharmaceutical Design ◽

10.2174/1381612825666190115122622 ◽

2019 ◽

Vol 24 (40) ◽

pp. 4742-4754 ◽

Cited By ~ 3

Author(s):

Raji Lenin ◽

Samuel M. Thomas ◽

Rajashekhar Gangaraju

Keyword(s):

Oxidative Stress ◽

Strong Association ◽

Neurovascular Unit ◽

Plasma Concentrations ◽

Endothelial Activation ◽

Retinal Diseases ◽

Respiratory Chain Complexes ◽

Blood Retinal Barrier ◽

Tnf Α ◽

And Oxidative Stress

Background: The eye is considered as a window of the disease, and a better understanding of neurodegenerative changes in the eye may help diagnose and manage neurodegenerative diseases including the diseases of brain, heart, kidney and liver. In the eye, the blood retinal barrier (BRB] is maintained by a combination of endothelial cells, pericytes, and glia. This BRB integrity is fundamental to the physiology of retinal cellular function and accurate vision. The role of endothelial dysfunction as a consequence of endothelial activation in the initiation and prolongation of neurovascular diseases of the retina is emerging. Methods: The observations made in this article are a result of our research over the years in the subject matter and also based on a literature search using PubMed with keywords including but not limited to endothelial, permeability, oxidative stress, ROS, TNF-α, retina, injury, and neurodegeneration. Several studies were identified that fulfilled the inclusion criteria. Overall, published studies support an association between endothelial activation, inflammation and oxidative stress in retinal diseases. Although the selection of specific endothelial activation biomarkers in the retina is less clear, there is an increased association between inflammation in the severity of diabetic retinopathy. Studies in other clinically relevant studies demonstrated a strong association of endothelial activation to alterations in mitochondrial respiratory chain complexes, pericyte integrity, microglial activation, neutrophil extracellular traps and elevated plasma concentrations of TNF-α. Conclusion: The compromise in BRB as a consequence of the neurovascular unit in the retinal tissue has gained a lot of attention and studies addressing these should result in a better understanding of the pathophysiology of retinal diseases. Although there are no specific retinal markers of endothelial activation and inflammation, future studies using specific models that display endothelial activation, inflammation and oxidative stress likely yield better understanding on the cause or effect relationship of endothelial activation in retinal diseases.

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Interaction between TNF-α and oxidative stress status in first-episode drug-naïve schizophrenia

Psychoneuroendocrinology ◽

10.1016/j.psyneuen.2020.104595 ◽

2020 ◽

Vol 114 ◽

pp. 104595 ◽

Cited By ~ 6

Author(s):

Shiguang Zhu ◽

Lei Zhao ◽

Yong Fan ◽

Qinyu Lv ◽

Kang Wu ◽

...

Keyword(s):

Oxidative Stress ◽

First Episode ◽

Tnf Α ◽

Oxidative Stress Status ◽

Drug Naïve ◽

And Oxidative Stress

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Neurotrophins, cytokines, oxidative stress mediators and mood state in bipolar disorder: systematic review and meta-analyses

The British Journal of Psychiatry ◽

10.1192/bjp.2018.144 ◽

2018 ◽

Vol 213 (3) ◽

pp. 514-525 ◽

Cited By ~ 36

Author(s):

Tobias Rowland ◽

Benjamin I. Perry ◽

Rachel Upthegrove ◽

Nicholas Barnes ◽

Jayanta Chatterjee ◽

...

Keyword(s):

Oxidative Stress ◽

Systematic Review ◽

Bipolar Disorder ◽

Inflammatory Markers ◽

Healthy Controls ◽

Oxidative Stress Markers ◽

Stress Markers ◽

Tnf Α ◽

Meta Analyses ◽

And Oxidative Stress

BackgroundA reliable biomarker signature for bipolar disorder sensitive to illness phase would be of considerable clinical benefit. Among circulating blood-derived markers there has been a significant amount of research into inflammatory markers, neurotrophins and oxidative stress markers.AimsTo synthesise and interpret existing evidence of inflammatory markers, neurotrophins and oxidative stress markers in bipolar disorder focusing on the mood phase of illness.MethodFollowing PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a systematic review was conducted for studies investigating peripheral biomarkers in bipolar disorder compared with healthy controls. We searched Medline, Embase, PsycINFO, SciELO and Web of Science, and separated studies by bipolar mood phase (mania, depression and euthymia). Extracted data on each biomarker in separate mood phases were synthesised using random-effects model meta-analyses.ResultsIn total, 53 studies were included, comprising 2467 cases and 2360 controls. Fourteen biomarkers were identified from meta-analyses of three or more studies. No biomarker differentiated mood phase in bipolar disorder individually. Biomarker meta-analyses suggest a combination of high-sensitivity C-reactive protein/interleukin-6, brain derived neurotrophic factor/tumour necrosis factor (TNF)-α and soluble TNF-α receptor 1 can differentiate specific mood phase in bipolar disorder. Several other biomarkers of interest were identified.ConclusionsCombining biomarker results could differentiate individuals with bipolar disorder from healthy controls and indicate a specific mood-phase signature. Future research should seek to test these combinations of biomarkers in longitudinal studies.Declaration of interestNone.

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Inhibition of microRNA-155 Alleviates Neurological Dysfunction Following Transient Global Ischemia and Contribution of Neuroinflammation and Oxidative Stress in the Hippocampus

Current Pharmaceutical Design ◽

10.2174/1381612825666190926162229 ◽

2020 ◽

Vol 25 (40) ◽

pp. 4310-4317 ◽

Cited By ~ 4

Author(s):

Lichao Sun ◽

Shouqin Ji ◽

Jihong Xing

Keyword(s):

Oxidative Stress ◽

Brain Edema ◽

Severity Score ◽

Global Ischemia ◽

Signal Pathways ◽

Neurological Severity Score ◽

Tnf Α ◽

Transient Global Ischemia ◽

And Oxidative Stress

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

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Febuxostat Attenuates the Progression of Periodontitis in Rats

Pharmacology ◽

10.1159/000513034 ◽

2021 ◽

pp. 1-11

Author(s):

Naseratun Nessa ◽

Miyuki Kobara ◽

Hiroe Toba ◽

Tetsuya Adachi ◽

Toshiro Yamamoto ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Bone Resorption ◽

Alveolar Bone ◽

Alveolar Bone Loss ◽

Gingival Tissue ◽

Systemic Effects ◽

Rt Pcr ◽

Tnf Α ◽

And Oxidative Stress

Introduction: Periodontitis is a lifestyle-related disease that is characterized by chronic inflammation in gingival tissue. Febuxostat, a xanthine oxidase inhibitor, exerts anti-inflammatory and antioxidant effects. Objective: The present study investigated the effects of febuxostat on periodontitis in a rat model. Methods: Male Wistar rats were divided into 3 groups: control, periodontitis, and febuxostat-treated periodontitis groups. Periodontitis was induced by placing a ligature wire around the 2nd maxillary molar and the administration of febuxostat (5 mg/kg/day) was then initiated. After 4 weeks, alveolar bone loss was assessed by micro-computed tomography and methylene blue staining. The expression of osteoprotegerin (OPG), a bone resorption inhibitor, was detected by quantitative RT-PCR and immunological staining, and the number of osteoclasts in gingival tissue was assessed by tartrate-resistant acid phosphatase staining. The mRNA and protein expression levels of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), in gingival tissue were measured using quantitative RT-PCR and immunological staining. Oxidative stress in gingival tissue was evaluated by the expression of 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2-deoxyguanosine (8-OHdG). To clarify the systemic effects of periodontitis, blood pressure and glucose tolerance were examined. Results: In rats with periodontitis, alveolar bone resorption was associated with reductions in OPG and increases in osteoclast numbers. The gingival expression of TNF-α, IL-1β, 4-HNE, and 8-OHdG was up-regulated in rats with periodontitis. Febuxostat significantly reduced alveolar bone loss, proinflammatory cytokine levels, and oxidative stress. It also attenuated periodontitis-induced glucose intolerance and blood pressure elevations. Conclusion: Febuxostat prevented the progression of periodontitis and associated systemic effects by inhibiting proinflammatory mediators and oxidative stress.

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Targeting ROS/NF-κB sigaling pathway by the seedless black Vitis vinifera polyphenols in CCl4-intoxicated kidney, lung, brain, and spleen in rats

Scientific Reports ◽

10.1038/s41598-021-96008-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Noha H. Habashy ◽

Ahmad S. Kodous ◽

Marwa M. Abu-Serie

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Vitis Vinifera ◽

Rat Kidney ◽

Environmental Pollutant ◽

Enhancing Effect ◽

Tnf Α ◽

Cox 2 ◽

Histopathological Studies ◽

And Oxidative Stress

AbstractCarbon tetrachloride (CCl4) is an abundant environmental pollutant that can generate free radicals and induce oxidative stress in different human and animal organs like the kidney, lung, brain, and spleen, causing toxicity. The present study evaluated the alleviative mechanism of the isolated polyphenolic fraction from seedless (pulp and skin) black Vitis vinifera (VVPF) on systemic oxidative and necroinflammatory stress in CCl4-intoxicated rats. Here, we found that the administration of VVPF to CCl4-intoxicated rats for ten days was obviously ameliorated the CCl4-induced systemic elevation in ROS, NO and TBARS levels, as well as MPO activity. Also, it upregulated the cellular activities of the enzymatic (SOD, and GPx) and non-enzymatic (TAC and GSH) antioxidants. Furthermore, the gene expression of the ROS-related necroinflammatory mediators (NF-κB, iNOS, COX-2, and TNF-α) in the kidney, brain, and spleen, as well as IL-1β, and IL-8 in the lung were greatly restored. The histopathological studies confirmed these biochemical results and showed a noticeable enhancing effect in the architecture of the studied organs after VVPF intake. Thus, this study indicated that VVPF had an alleviative effect on CCl4-induced necroinflammation and oxidative stress in rat kidney, lung, brain, and spleen via controlling the ROS/NF-κB pathway.

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