Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes

OBJECTIVE AND METHOD: There is a growing amount of data indicating that alterations in brain-derived neurotrophic factor and increased oxidative stress may play a role in the pathophysiology of bipolar disorder. In light of recent evidence demonstrating that brain-derived neurotrophic factor levels are decreased in situations of increased oxidative stress, we have examined the correlation between serum thiobarbituric acid reactive substances, a measure of lipid peroxidation, and serum brain-derived neurotrophic factor levels in bipolar disorder patients during acute mania and in healthy controls. RESULTS: Serum thiobarbituric acid reactive substances and brain-derived neurotrophic factor levels were negatively correlated in bipolar disorder patients (r = -0.56; p = 0.001), whereas no significant correlation was observed in the control group.. CONCLUSION: These results suggest that alterations in oxidative status may be mechanistically associated with abnormal low levels of brain-derived neurotrophic factor observed in individuals with bipolar disorder.

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Association Between Magnesium and Oxidative Stress in Patients with Obesity

Current Nutrition & Food Science ◽

10.2174/1573401315666190730123842 ◽

2020 ◽

Vol 16 (5) ◽

pp. 743-748

Author(s):

Ana R.S. de Oliveira ◽

Kyria J.C. Cruz ◽

Jennifer B.S. Morais ◽

Juliana S. Severo ◽

Jéssica B. Beserra ◽

...

Keyword(s):

Oxidative Stress ◽

Thiobarbituric Acid ◽

Magnesium Concentration ◽

Control Group ◽

Compensatory Mechanism ◽

Thiobarbituric Acid Reactive Substances ◽

Magnesium Intake ◽

Significant Difference ◽

Dietary Magnesium ◽

And Control

Background: The role of minerals in preventing the generation of oxidative stress in obese individuals has been evaluated. Magnesium is an antioxidant nutrient and a cofactor of enzymes involved in the cell membrane stabilization, attenuating the effects of oxidative stress. Objective: To evaluate the association between magnesium and concentrations of thiobarbituric acid reactive substances (TBARS) in patients with obesity and eutrophic women. Methods: A cross-sectional study was conducted with 73 women, divided into two groups: case group (patients with obesity, n=27) and control group (eutrophic women, n=46). Measurements of body mass index and waist circumference were performed. Dietary magnesium intake was assessed by the three-day food record using the NutWin software. Urinary magnesium concentration was measured by atomic absorption spectrophotometry method. Plasma concentrations of thiobarbituric acid reactive substances (TBARS) were also determined. Results: Mean values of dietary magnesium intake were 161.59 ± 60.04 and 158.73 ± 31.96 for patients with obesity and control group, respectively, with no significant difference between the groups studied (p >0.05). The value of urinary excretion of magnesium was lower than the reference values in both groups, with no significant difference between the groups studied (p >0.05). The plasma concentration of thiobarbituric acid reactive substances was significantly higher in patients with obesity compared to the control group (p <0.001). There was no correlation between levels of magnesium biomarkers and the concentration of TBARS (p >0.05). Conclusion: Patients with obesity showed a reduced dietary magnesium intake which seems to induce hypomagnesuria as a compensatory mechanism. The marker of oxidative stress evaluated in this study was not influenced by magnesium.

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Brain-derived neurotrophic factor levels in newly diagnosed patients with bipolar disorder, their unaffected first-degree relatives and healthy controls

BJPsych Open ◽

10.1192/bjo.2021.9 ◽

2021 ◽

Vol 7 (2) ◽

Author(s):

Nanna Aagaard Petersen ◽

Marc Østergaard Nielsen ◽

Klara Coello ◽

Sharleny Stanislaus ◽

Sigurd Melbye ◽

...

Keyword(s):

Bipolar Disorder ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Newly Diagnosed ◽

First Degree Relatives ◽

Duration Of Illness ◽

And Gender ◽

Medication Status

Background Brain-derived neurotrophic factor (BDNF), which facilitates neuroplasticity and synaptogenesis, may be decreased in bipolar disorder, but has not been systematically investigated in people with newly diagnosed bipolar disorder and unaffected first-degree relatives. Aims To compare BDNF levels in patients with newly diagnosed bipolar disorder, their unaffected first-degree relatives and healthy controls. Method The study investigated plasma BDNF levels in patients (n = 371) with newly diagnosed bipolar disorder, their unaffected first-degree relatives (n = 98) and healthy controls (n = 200) using enzyme-linked immunosorbent assay. We further investigated associations between BDNF levels and illness-related variables and medication status. Results BDNF levels were found to be 22.0% (95% CI 1.107–1.343) higher in patients with bipolar disorder compared with healthy controls (P < 0.001) and 15.6% higher in unaffected first-degree relatives compared with healthy controls (95% CI 1.007–1.327, P = 0.04), when adjusting for age and gender. Further, BDNF levels were positively associated with duration of illness at a trend level (P = 0.05), age (P = 0.001) and use of anti-epileptic medication (P = 0.05). Conclusions These findings suggest that BDNF levels are not decreased in the early stages of bipolar disorder and in unaffected first-degree relatives contrasting with prior findings during later stages of the illness.

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Urinary Nitric Oxide Metabolites and Lipid Peroxidation By-Products in Migraine

Cephalalgia ◽

10.1046/j.1468-2982.2003.00447.x ◽

2003 ◽

Vol 23 (1) ◽

pp. 39-42 ◽

Cited By ~ 56

Author(s):

I Ciancarelli ◽

MG Tozzi-Ciancarelli ◽

C Di Massimo ◽

C Marini ◽

A Carolei

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Migraine Attack ◽

Superoxide Anion ◽

Thiobarbituric Acid ◽

Healthy Controls ◽

Thiobarbituric Acid Reactive Substances ◽

Flow Changes ◽

Nitric Oxide Metabolites ◽

By Products

Enhanced endothelium nitric oxide (NO) and superoxide anion release may cause migraine through related cerebral blood flow changes. Thirty subjects suffering from migraine with and without aura and 20 healthy controls were investigated. Urine samples collected for 24 h during and after the migraine attack, and during the headache-free period, were assayed for urinary NO stable metabolites (NOx) and thiobarbituric acid reactive substances (TBARS). During the headache-free period urinary NOx and TBARS levels were higher in migraine sufferers than in controls (NOx 0.77 ± 0.14 vs. 0.28 ± 0.15 mmol/mmol creatinine, P < 0.05; TBARS 0.40 ± 0.19 vs. 0.26 ± 0.13 μmol/mol creatinine, P < 0.05). Also, NOx excretion was higher during the headache-free period than during or after the migraine attack ( P < 0.05). Urinary TBARS were increased during the attack with respect to the headache-free period ( P < 0.05). No differences were observed in the same parameters between sufferers of migraine with and without aura. Urinary NOx and TBARS might be promising as markers of their systemic levels to evaluate the increased vulnerability to oxidative stress in migraine sufferers.

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The effects of hydraulic calcium silicate containing endodontic materials on oxidative stress in erythrocytes and liver

Turkish Journal of Biochemistry ◽

10.1515/tjb-2016-0263 ◽

2017 ◽

Vol 43 (3) ◽

pp. 333-341 ◽

Cited By ~ 1

Author(s):

Kadriye Demirkaya ◽

Birsen Can Demirdöğen ◽

Zeynep Öncel Torun ◽

Onur Erdem ◽

Yaşar Meriç Tunca

Keyword(s):

Oxidative Stress ◽

Calcium Silicate ◽

Thiobarbituric Acid ◽

Control Group ◽

Antioxidant Enzyme Activities ◽

Thiobarbituric Acid Reactive Substances ◽

Dental Cement ◽

Oxidative Stress Parameters ◽

Liver Tbars ◽

Stress Parameters

Abstract Objective: The aim of this study was to evaluate the effects of hydraulic calcium silicate endodontic cements, MTA Angelus, MTA Fillapex, and Theracal LC, on erythrocyte and liver oxidative stress parameters of rats. Methods: Right upper incisor of each rat was extracted and polyethylene tubes containing the dental cements, or left empty for the control group, were inserted into the extraction socket. Blood and liver samples of each animal were obtained after 7, 30, or 60 days. Thiobarbituric acid reactive substances (TBARS) levels and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were determined by spectrophotometry. Results: Erythrocyte and liver TBARS levels, and CAT and SOD enzymatic activities were significantly increased in dental cement applied groups compared with controls on day 7. The highest erythrocyte and liver TBARS concentrations were observed in the MTA Angelus group on day 7 of exposure. On day 30, erythrocyte CAT activity remained markedly high, but the other parameters returned to almost normal levels. On day 60, all parameters were similar between the control and the experimental groups. Conclusions: This is the first study to show that TBARS levels and antioxidant enzyme activities are transiently increased as a result of dental cement application.

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Correlation between Peripheral Levels of Brain-Derived Neurotrophic Factor and Hippocampal Volume in Children and Adolescents with Bipolar Disorder

Neural Plasticity ◽

10.1155/2015/324825 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Tatiana Lauxen Peruzzolo ◽

Mauricio Anes ◽

Andre de Moura Kohmann ◽

Ana Claudia Mércio Loredo Souza ◽

Ramiro Borges Rodrigues ◽

...

Keyword(s):

Bipolar Disorder ◽

Children And Adolescents ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Hippocampal Volume ◽

Pediatric Bipolar Disorder ◽

Control Group ◽

Drug Naïve ◽

Short Time ◽

The Brain

Pediatric bipolar disorder (PBD) is a serious mental disorder that affects the development and emotional growth of affected patients. The brain derived neurotrophic factor (BDNF) is recognized as one of the possible markers of the framework and its evolution. Abnormalities in BDNF signaling in the hippocampus could explain the cognitive decline seen in patients with TB. Our aim with this study was to evaluate possible changes in hippocampal volume in children and adolescents with BD and associate them to serum BDNF. Subjects included 30 patients aged seven to seventeen years from the ProCAB (Program for Children and Adolescents with Bipolar Disorder). We observed mean right and left hippocampal volumes of 41910.55 and 41747.96 mm3, respectively. No statistically significant correlations between peripheral BDNF levels and hippocampal volumes were found. We believe that the lack of correlation observed in this study is due to the short time of evolution of BD in children and adolescents. Besides studies with larger sample sizes to confirm the present findings and longitudinal assessments, addressing brain development versus a control group and including drug-naive patients in different mood states may help clarify the role of BDNF in the brain changes consequent upon BD.

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Changes in Brain-Derived Neurotrophic Factor Following Treatment with Mifepristone in Bipolar Disorder and Schizophrenia

Australian & New Zealand Journal of Psychiatry ◽

10.1080/00048670701213211 ◽

2007 ◽

Vol 41 (4) ◽

pp. 321-326 ◽

Cited By ~ 35

Author(s):

Paul Mackin ◽

Peter Gallagher ◽

Stuart Watson ◽

Allan H. Young ◽

I. Nicol Ferrier

Keyword(s):

Bipolar Disorder ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Crossover Design ◽

Healthy Controls ◽

Double Blind ◽

Beneficial Effects ◽

Before And After ◽

Patient Groups ◽

Cortisol Levels

Objective: Brain-derived neurotrophic factor (BDNF) is stress-responsive and has been implicated in a number of disparate neuropsychiatric disorders. Glucocorticoid antagonists have been shown to have beneficial effects on mood and cognitive function in bipolar disorder but not in schizophrenia. The aim of the present study was to investigate BDNF levels in patients with bipolar disorder and schizophrenia before and after treatment with the glucocorticoid receptor antagonist mifepristone. Methods: Peripheral BDNF levels were measured in patients with bipolar disorder (n=20), schizophrenia (n=20) and 14 matched healthy controls following 7 days of adjunctive mifepristone (600 mg day−1) treatment in a double-blind, placebo-controlled crossover design study. Results: Baseline BDNF values were similar in both patient groups and in healthy controls. Following treatment with mifepristone, cortisol levels were significantly increased and BDNF levels decreased in both schizophrenia and bipolar disorder. A significant correlation existed between change in cortisol level and change in BDNF levels following mifepristone treatment in schizophrenia, but not in bipolar disorder. Conclusion: Differing BDNF responses to increasing cortisol levels between patients with schizophrenia and with bipolar disorder may reflect underlying pathophysiological mechanisms.

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Altered plasma glutathione levels in bipolar disorder indicates higher oxidative stress; a possible risk factor for illness onset despite normal brain-derived neurotrophic factor (BDNF) levels

Psychological Medicine ◽

10.1017/s0033291714000014 ◽

2014 ◽

Vol 44 (11) ◽

pp. 2409-2418 ◽

Cited By ~ 48

Author(s):

A. R. Rosa ◽

N. Singh ◽

E. Whitaker ◽

M. de Brito ◽

A. M. Lewis ◽

...

Keyword(s):

Oxidative Stress ◽

Bipolar Disorder ◽

Neurotrophic Factor ◽

Redox State ◽

Brain Derived Neurotrophic Factor ◽

Normal Brain ◽

Total Glutathione ◽

Illness Onset ◽

Plasma Glutathione ◽

Bipolar Patients

BackgroundOxidative stress and neurotrophic factors have been implicated in the pathophysiology of bipolar disorder. Our objective was to determine whether plasma glutathione or brain-derived neurotrophic factor (BDNF) levels were abnormal in bipolar disorder and therefore useful as possible biomarkers.MethodBlood samples were collected from subsyndromal, medicated bipolar I patients (n = 50), recruited from OXTEXT, University of Oxford, and from 50 matched healthy controls. Total and oxidized glutathione levels were measured using an enzymatic recycling method and used to calculate reduced, percentage oxidized, ratio of reduced:oxidized and redox state. BDNF was measured using an enzyme-linked immunoassay. Self-monitored mood scores for the bipolar group were available (Quick Inventory of Depressive Symptomatology and the Altman Self-Rating Mania Scale) over an 8-week period.ResultsCompared with controls, bipolar patients had significantly lower levels of total glutathione and it was more oxidized. BDNF levels were not different. Age of illness onset but not current mood state correlated with total glutathione levels and its oxidation status, so that lower levels of total and reduced glutathione were associated with later onset of disease, not length of illness.ConclusionsPlasma glutathione levels and redox state detect oxidative stress even in subsyndromal patients with normal BDNF. It may relate to the onset and development of bipolar disorder. Plasma glutathione appears to be a suitable biomarker for detecting underlying oxidative stress and for evaluating the efficacy of antioxidant intervention studies.

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Evaluation of total oxidative status and total antioxidant capacity in patients with endemic fluorosis

Toxicology and Industrial Health ◽

10.1177/0748233711428641 ◽

2011 ◽

Vol 29 (2) ◽

pp. 175-180 ◽

Cited By ~ 16

Author(s):

Ercan Varol ◽

Atilla Icli ◽

Fatih Aksoy ◽

Hasan Aydin Bas ◽

Recep Sutcu ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Capacity ◽

Total Antioxidant Capacity ◽

Oxidative Status ◽

Stress Index ◽

Control Group ◽

Healthy Controls ◽

Endemic Fluorosis ◽

Total Antioxidant ◽

Total Oxidative Status

The objective of the present study was to determine the plasma total oxidative status (TOS) and total antioxidant capacity (TAC) in patients with endemic fluorosis. A total of 79 (35 males and 44 females; mean age 44.0 ± 11.9 years) patients with endemic fluorosis and 55 (23 males and 32 females; mean age 48.3 ± 8.5 years) age-, sex- and body mass index-matched healthy controls were included in this study. The urine fluoride levels and plasma TOS and TAC levels were measured. The urine fluoride levels of fluorosis patients were significantly higher than control subjects as expected (1.91 ± 0.15 vs. 0.49 ± 0.13 mg/L, respectively; p < 0.001). TOS was significantly higher in fluorosis group than in control group (17.55 ± 3.82 vs. 15.06 ± 4.31 μmol H2O2 Eq/L, respectively; p = 0.001). TAC was significantly lower in fluorosis group than in control group (1.60 ± 0.36 vs. 1.82 ± 0.51 mmol Trolox Eq/L, respectively; p = 0.004). Oxidative stress index (OSI) was significantly higher in fluorosis group than in control group (11.5 ± 3.8 vs. 8.8 ± 3.7, respectively; p < 0.001). Correlation analysis in all the groups indicated that TAC was negatively correlated with urine fluoride ( r = −0.25, p = 0.003), TOS was positively correlated with urine fluoride ( r = 0.34, p < 0.001) and OSI was positively correlated with urine fluoride ( r = 0.36, p < 0.001). The results of our study demonstrate that oxidative stress plays an important role in the pathogenesis of the endemic fluorosis.

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Serum levels of brain-derived neurotrophic factor and thiobarbituric acid reactive substances in chronically medicated schizophrenic patients: a positive correlation

Brazilian Journal of Psychiatry ◽

10.1590/s1516-44462008000400006 ◽

2008 ◽

Vol 30 (4) ◽

pp. 337-340 ◽

Cited By ~ 23

Author(s):

Clarissa Severino Gama ◽

Michael Berk ◽

Ana Cristina Andreazza ◽

Flávio Kapczinski ◽

Paulo Belmonte-de-Abreu

Keyword(s):

Superoxide Dismutase ◽

Antioxidant Enzymes ◽

Neurotrophic Factor ◽

Thiobarbituric Acid ◽

Serum Levels ◽

Brain Derived Neurotrophic Factor ◽

Thiobarbituric Acid Reactive Substances ◽

Positive Correlation ◽

Oxidative Markers ◽

Schizophrenic Patients

OBJECTIVE: The neurotrophins, antioxidant enzymes and oxidative markers have reciprocal interactions. This report verified in chronically stable medicated schizophrenic patients whether there are correlations between the serum levels of superoxide dismutase, a key enzyme in the antioxidant defense, thiobarbituric acid reactive substances, a direct index of lipid peroxidation, and brain-derived neurotrophic factor, the most widely distributed neurotrophin. METHOD: Sixty DSM-IV schizophrenic patients were included (43 males, 17 females). Mean age was 34.7 ± 10.8 years, mean age at first episode was 19.8 ± 7.9 years, and mean illness duration was 14.9 ± 8.5 years. Each subject had a blood sample collected for the determination of serum levels of brain-derived neurotrophic factor, thiobarbituric acid reactive substances and superoxide dismutase. RESULTS: Brain-derived neurotrophic factor levels showed a positive correlation with thiobarbituric acid reactive substances levels (r = 0.333, p = 0.009). Brain-derived neurotrophic factor levels were not correlated with superoxide dismutase levels (r = - 0.181, p = 0.166), and superoxide dismutase levels were not correlated with thiobarbituric acid reactive substances levels (r = 0.141, p = 0.284). CONCLUSIONS: The positive correlation between brain-derived neurotrophic factor and thiobarbituric acid reactive substances suggests the need of further investigation on intracellular interactions of neurotrophins, antioxidant enzymes and oxidative markers. In addition, this opens a venue for investigation on treatments for the prevention of neurotoxicity along the course of schizophrenia.

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Flunarizine Effects on Oxidative Stress in Migraine Patients

Cephalalgia ◽

10.1111/j.1468-2982.2003.00705.x ◽

2004 ◽

Vol 24 (7) ◽

pp. 528-532 ◽

Cited By ~ 17

Author(s):

I Ciancarelli ◽

MG Tozzi-Ciancarelli ◽

C Di Massimo ◽

C Marini ◽

A Carolei

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Migraine Without Aura ◽

Antioxidant Properties ◽

Thiobarbituric Acid ◽

Healthy Controls ◽

Thiobarbituric Acid Reactive Substances ◽

Oxidative Reactions ◽

Urinary Levels ◽

Before And After

Prophylactic activity of flunarizine in migraine is attributed to its antioxidant properties and to the relief of cerebral vasospasm in which nitric oxide (NO) is involved. We investigated the antimigraine activity of flunarizine and its influence on NO and oxidative marker bioavailability in 25 subjects suffering from migraine without aura and in 25 healthy controls. Urinary samples collected before and after treatment with flunarizine (5 mg orally per day for 6 months) were assayed for NO stable metabolites (NOx) and thiobarbituric acid reactive substances (TBARS). Urinary levels of NOx and TBARS were higher in migraine sufferers before treatment than in healthy controls. No differences were observed in NOx levels in migraine sufferers, before and after flunarizine treatment; urinary TBARS levels were decreased after flunarizine treatment ( P < 0.05) and remained persistently higher than in healthy controls ( P < 0.05). Our results suggest that flunarizine did not prevent NO-mediated vasodilatation, while it proved effective in limiting the oxidative reactions occurring in migraine sufferers.

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