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BACKGROUND: Hypertension, atherogenicity and insulin resistance are major risk factors of cardiovascular disorder (CVD), which shows a strong comorbidity with major depression (MDD) and bipolar disorder (BD). Activated oxidative and nitrosative stress (O&NS), inflammatory pathways, and increased atherogenicity are shared pathways underpinning CVD and mood disorders. METHODS: The current study examined the effects of lipid hydroperoxides (LOOH), superoxide dismutase (SOD), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), and malondialdehyde (MDA) on systolic (SBP) and diastolic (DBP) blood pressure in 96 mood disordered patients and 60 healthy controls. RESULTS: A large part of the variance in SBP (31.6%) was explained by the regression on a z unit-weighted composite score (based on LOOH, AOPP, SOD, NOx) reflecting nitro-oxidative stress toxicity (NOSTOX), coupled with highly sensitive C-reactive protein, body weight and use of antihypertensives. Increased DBP was best predicted (23.8%) by body mass index and NOSTOX. The most important O&NS biomarkers predicting an increased SBP were in descending order of significance: LOOH, AOPP and SOD. Higher levels of the atherogenic index of plasma, HOMA2 insulin resistance index and basal thyroid-stimulating hormone also contributed to increased SBP independently from NOSTOX. Although there were no significant changes in SBP/DBP in mood disorders, the associations between NOSTOX and blood pressure were significant in patients with mood disorders but not in healthy controls. CONCLUSIONS: Activated O&NS pathways including increased lipid peroxidation and protein oxidation, which indicates hypochlorous stress, are the most important predictors of an increased BP, especially in patients with mood disorders.
Assuntos
Hipertensão , Transtornos do Humor , Produtos da Oxidação Avançada de Proteínas/metabolismo , Biomarcadores/metabolismo , Pressão Sanguínea , Humanos , Estresse OxidativoRESUMO
Many fruits and vegetables contain compounds with antioxidant properties, but the processing and storage conditions of the food industry may damage these beneficial compounds and produce free radicals that are associated with oxidative stress. This study aims to evaluate in vitro the antioxidant capacity and prooxidant effects of juçara pulp fermented with Lactobacillus reuteri or Lactobacillus plantarum before and after spray-drying with maltodextrin, gum arabic or gelatin and stored at 25 °C for 90 days. The antioxidant capacity was assessed by measuring the ability to scavenge reactive oxygen species (ROS) in the neutrophil respiratory burst and free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH), and by determining the total phenolic content. The prooxidant effects were analyzed as free radical formation measured by electronic paramagnetic resonance (EPR). Fermentation by both bacteria increased the antioxidant activity, while the spray-drying process decreased the content of phenolic compounds (65-85%) and the DPPH scavenging ability, depending on the carrier usage. All of the samples inhibited ROS in the neutrophil burst, and the juçara pulp fermented by L. reuteri and dried with gum arabic exhibited the best performance. Spray-drying did not influence the intensity or type of free radicals detected by EPR. However, storage at room temperature decreased the antioxidant capacity and increased free radical formation.
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BACKGROUND: Silver sulfadiazine (SSD) has been widely used in burned patients for the prevention of local infections. To be biologically active and exert antimicrobial properties, silver needs to be present in the form of silver ions (Ag1+) that bind to negatively charged proteins, namely, the RNA and DNA in microorganisms. However, previous published studies conducted with SSD in the 1990s reported a high level of silver absorption through damaged skin and noted the potential cytotoxicity of Ag1+ to human cells. SSD toxicity, however, had been described in cell cultures using arbitrary silver concentrations. In the present study, we determined the serum silver levels in burned patients treated with SSD and, taking into account the molar Ag1+ concentrations found in these patients, we evaluated the Ag1+ toxicity effects on inflammatory cells (ROS and cytokine production) in vitro. METHODS: Twenty patients with an average burned body surface area of 27.68% were included in this study. RESULTS: Patients' Ag1+ serum levels reached up to 558 times those of the unexposed controls. Ag1+ was then added to inflammatory cells in vitro at levels up to 2000 times the level of the control, and there was no effect on the viability of the cells nor on the rate of apoptosis. We observed a decrease in reactive oxygen species production by mononuclear (MN) and polymorphonuclear (PMN) cells, as well as a substantial decrease in cytokines IL-1ß, IL-6, IL-8, IL-10, and TNF-α production by leukocytes (MN and PNM). CONCLUSION: These findings suggest that Ag1+ may contribute to negative outcomes after burns, decreasing the primary defense mechanism (respiratory burst) and altering cytokine production.
Assuntos
Anti-Infecciosos Locais/toxicidade , Anti-Infecciosos Locais/uso terapêutico , Queimaduras/tratamento farmacológico , Leucócitos Mononucleares/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Nitrato de Prata/toxicidade , Sulfadiazina de Prata/uso terapêutico , Prata/sangue , Adulto , Apoptose/efeitos dos fármacos , Superfície Corporal , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Técnicas In Vitro , Interleucina-10/metabolismo , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/efeitos dos fármacos , Interleucina-8/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Although, staging models gained momentum to stage define affective disorders, no attempts were made to construct mathematical staging models using clinical and biomarker data in patients with major depression and bipolar disorder. The aims of this study were to use clinical and biomarker data to construct statistically derived staging models, which are associated with early lifetime traumata (ELTs), affective phenomenology, and biomarkers. In the current study, 172 subjects participated, 105 with affective disorders (both bipolar and unipolar) and 67 controls. Staging scores were computed by extracting latent vectors (LVs) from clinical data including ELTs, recurring flare ups and suicidal behaviors, outcome data such as disabilities and health-related quality of life (HR-QoL), and paraoxonase (PON)1 actvities and nitro-oxidative stress biomarkers. Recurrence of episodes and suicidal behaviors could reliably be combined into a LV with adequate composite reliability (the "recurrence LV"), which was associated with female sex, the combined effects of multiple ELTs, disabilities, HR-QoL, and impairments in cognitive tests. All those factors could be combined into a reliable "ELT-staging LV" which was significantly associated with nitro-oxidative stress biomarkers. A reliable LV could be extracted from serum PON1 activities, recurrent flare ups, disabilities, and HR-QoL. Our ELT-staging index scores the severity of a relevant affective dimension, shared by both major depression and bipolar disorder, namely the trajectory from ELTs, a relapsing course, and suicidal behaviors to progressive disabilities. Patients were classified into three stages, namely an early stage, a relapse-regression stage, and a suicidal-regression stage. Lowered lipid-associated antioxidant defenses may be a drug target to prevent the transition from the early to the later regression stages.
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Antioxidantes/metabolismo , Lipídeos/química , Modelos Biológicos , Transtornos do Humor/patologia , Estresse Oxidativo , Algoritmos , Humanos , Análise dos Mínimos Quadrados , Recidiva , SuicídioRESUMO
Objectives: Mood disorders (MDs) frequently co-exist with cardiovascular disease (CVD) and immune-inflammatory and oxidative stress are important shared pathophysiological pathways. Even though there has been an extensive investigation of the enzyme paraoxonase 1 (PON1) as a biomarker of susceptibility for CVD, there are few reports studying PON1 in MDs. The aim of this study was to determine the association between PON1 activities as well as functional genotypes and MD diagnosis, clinical characteristics and outcomes. Methods: PON1 activities and functional genotypes were assayed in 58 bipolar disorder (BD) and 32 major depressed patients (MDD) and compared with 59 controls. Results: Our findings show significantly lower PON1 total and CMPAase activities in MDs, which are partly related to the number of previous depressive and manic episodes. Lowered CMPAase activity is associated with a worse outcome of MDs as indicated by lowered quality of life (WHOQoL-BREF scale) and increased disability in the Sheeham scale. Conclusions: We hypothesise that lowered PON1 total and CMPAase activities may play a role in the pathophysiology of MDs by lowering antioxidant defences thereby increasing the risk of lipid peroxidation and inflammation; lowered inhibition of quorum-sensing lactones thereby increasing bacterial proliferation; and attenuated homocysteine thiolactone catabolism which may trigger immune-inflammatory response and/or induce neurotoxicity.
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Arildialquilfosfatase/metabolismo , Transtorno Bipolar/genética , Transtorno Depressivo Maior/genética , Adulto , Arildialquilfosfatase/genética , Biomarcadores/metabolismo , Estudos de Casos e Controles , Avaliação da Deficiência , Feminino , Genótipo , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Qualidade de Vida , RecidivaRESUMO
Background Early life trauma (ELT) may drive mood disorder phenomenology, nitro-oxidative pathways and impairments in semantic memory. There are no data regarding the impact of ELT on affective phenomenology and whether these pathways are mediated by staging or lowered lipid-associated antioxidant defences. Methods This study examined healthy controls (n=54) and patients with affective disorders including major depression, bipolar disorder and anxiety disorders (n=118). ELT was assessed using the Child Trauma Questionnaire. In addition, we measured affective phenomenology and assayed advanced oxidation protein products; malondialdehyde, paraoxonase 1 (CMPAase) activity, high-sensitivity C-reactive protein (hsCRP), and high-density lipoprotein (HDL) cholesterol. Results ELT was associated into with increased risk for mood and comorbid anxiety disorders and a more severe phenomenology, including staging characteristics, depression and anxiety severity, suicidal behaviours, type of treatments, disabilities, body mass index, smoking behaviour and hsCRP, as well as lowered health-related quality of life, antioxidant defences and semantic memory. The number of mood episodes and CMPAase/HDL-cholesterol levels could be reliably combined into a new vulnerability staging-biomarker index, which mediates in part the effects of ELT on affective phenomenology and oxidative stress. Moreover, the effects of female sex on mood disorders and affective phenomenology are mediated by ELT. Discussion The cumulative effects of different ELT drive many aspects of affective phenomenology either directly or indirectly through effects of staging and/or lipid-associated antioxidant defences. The results show that children, especially girls, with ELT are at great risk to develop mood disorders and more severe phenotypes of affective disorders.
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Maus-Tratos Infantis/psicologia , Transtornos do Humor/epidemiologia , Estresse Oxidativo , Trauma Psicológico/epidemiologia , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Transtornos do Humor/sangue , Transtornos do Humor/etiologia , Trauma Psicológico/complicaçõesRESUMO
Accumulating evidence shows that nitro-oxidative pathways play an important role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD) and maybe anxiety disorders. The current study aims to examine superoxide dismutase (SOD1), catalase, lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), malondialdehyde (MDA), glutathione (GSH), paraoxonase 1 (PON1), high-density lipoprotein cholesterol (HDL), and uric acid (UA) in participants with and without generalized anxiety disorder (GAD) co-occurring or not with BD, MDD, or tobacco use disorder. Z unit-weighted composite scores were computed as indices of nitro-oxidative stress driving lipid and protein oxidation. SOD1, LOOH, NOx, and uric acid were significantly higher and HDL and PON1 significantly lower in participants with GAD than in those without GAD. GAD was more adequately predicted by increased SOD + LOOH + NOx and lowered HDL + PON1 composite scores. Composite scores of nitro-oxidative stress coupled with aldehyde and AOPP production were significantly increased in participants with comorbid GAD + MDD as compared with all other study groups, namely MDD, GAD + BD, BD, GAD, and healthy controls. In conclusion, GAD is characterized by increased nitro-oxidative stress and lipid peroxidation and lowered lipid-associated antioxidant defenses, while increased uric acid levels in GAD may protect against aldehyde production and protein oxidation. This study suggests that increased nitro-oxidative stress and especially increased SOD1 activity, NO production, and lipid peroxidation as well as lowered HDL-cholesterol and PON1 activity could be novel drug targets for GAD especially when comorbid with MDD.
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Transtornos de Ansiedade/complicações , Transtorno Depressivo Maior/complicações , Peroxidação de Lipídeos/fisiologia , Óxido Nítrico/metabolismo , Estresse Oxidativo/fisiologia , Adulto , Produtos da Oxidação Avançada de Proteínas/metabolismo , Análise de Variância , Transtornos de Ansiedade/epidemiologia , Arildialquilfosfatase/metabolismo , Índice de Massa Corporal , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Lipoproteínas HDL/metabolismo , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Ácido Úrico/metabolismo , Adulto JovemRESUMO
RATIONALE, AIMS: Major affective disorders including bipolar disorder (BD) and major depressive disorder (MDD) are associated with impaired health-related quality of life (HRQoL). Oxidative stress and subtle thyroid abnormalities may play a pathophysiological role in both disorders. Thus, the current study was performed to examine whether neuro-oxidative biomarkers and thyroid-stimulating hormone (TSH) levels could predict HRQoL in BD and MDD. METHODS: This cross-sectional study enrolled 68 BD and 37 MDD patients and 66 healthy controls. The World Health Organization (WHO) QoL-BREF scale was used to assess 4 QoL subdomains. Peripheral blood malondialdehyde (MDA), advanced oxidation protein products, paraoxonaxe/CMPAase activity, a composite index of nitro-oxidative stress, and basal TSH were measured. RESULTS: In the total WHOQoL score, 17.3% of the variance was explained by increased advanced oxidation protein products and TSH levels and lowered CMPAase activity and male gender. Physical HRQoL (14.4%) was associated with increased MDA and TSH levels and lowered CMPAase activity. Social relations HRQoL (17.4%) was predicted by higher nitro-oxidative index and TSH values, while mental and environment HRQoL were independently predicted by CMPAase activity. Finally, 73.0% of the variance in total HRQoL was explained by severity of depressive symptoms, use of anticonvulsants, lower income, early lifetime emotional neglect, MDA levels, the presence of mood disorders, and suicidal ideation. CONCLUSIONS: These data show that lowered HRQoL in major affective disorders could at least in part result from the effects of lipid peroxidation, protein oxidation, lowered antioxidant enzyme activities, and higher levels of TSH.
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Produtos da Oxidação Avançada de Proteínas/análise , Malondialdeído/análise , Transtornos do Humor , Qualidade de Vida , Tireotropina/análise , Adulto , Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Correlação de Dados , Depressão/diagnóstico , Depressão/metabolismo , Feminino , Humanos , Masculino , Transtornos do Humor/diagnóstico , Transtornos do Humor/metabolismo , Transtornos do Humor/psicologia , Sistema Nervoso/metabolismo , Estresse Oxidativo , Escalas de Graduação Psiquiátrica , Fatores de RiscoRESUMO
Early life trauma (ELT) may increase the risk towards bipolar disorder (BD) and major depression (MDD), disorders associated with activated neuro-oxidative and neuro-nitrosative stress (O&NS) pathways. It has remained elusive whether ELTs are associated with O&NS and which ELTs are associated with distinct affective disorder phenotypes. This case-control study examined patients with BD (n = 68) and MDD (n = 37) and healthy controls (n = 66). The Child Trauma Questionnaire (CTQ) was used to assess specific ELT. We measured malondialdehyde (MDA), lipid hydroperoxides (LOOH), superoxide dismutase (SOD), catalase, advanced oxidation protein products (AOPP); NO metabolites (NOx), paraoxonase 1 activity, zinc, albumin, high density lipoprotein cholesterol and -SH groups and computed z-unit weighted composite scores. Physical neglect significantly predicts higher z-unit weighted composite scores of LOOH+SOD, LOOH+SOD+NOx, LOOH+SOD+NOx + MDA and LOOH+SOD+NOx + AOPP. Sexual abuse was associated with a significantly lower composite score of zinc+albumin+SH. Emotional abuse was associated with severity of depression and anxiety, number of depressive and manic episodes, alcohol and hypnotics use, lifetime suicidal behavior and lowered quality of life. Sexual abuse was associated with an increased risk towards BD, but not MDD. ELT, especially physical neglect, may drive increased (nitro-)oxidative stress coupled with lipid and protein oxidation, which - together with emotional abuse - may play a role in severity of illness, lowered quality of life and MDD. ELTs are also associated with the onset of BD, but this link did not appear to be related to activated O&NS pathways. These novel findings deserve confirmation in prospective studies.