Induction of brain injury and depression in rats by chronic unpredictable stress associated with the augmentation of nitrosative stress and apoptosis / Inducción de lesión cerebral y depresión en ratas por estrés crónico impredecible asociado con el aumento del estrés nitrosativo y la apoptosis

SUMMARY: Repeated stress is a risk factor for memory impairment and neurological abnormalities in both humans and animals. We sought to investigate the extent of (i) brain tissue injury; (ii) nitrosative and oxidative stress in brain tissue homogenates; (iii) apoptotic and survival biomarkers in brain tissue homogenates; and (iv) immobility and climbing abilities, induced over a period of three weeks by chronic unpredictable stress (CUS). Wistar rats were either left untreated (Control group) or exposed to a variety of unpredictable stressors daily before being sacrificed after 3 weeks (model group). Assessment of depression-like behavior was performed and animals were then culled and harvested brain tissues were stained with basic histological staining and examined under light microscopy. In addition, brain tissue homogenates were prepared and assayed for these parameters; inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), superoxide dismutase (SOD), caspase-3, and B-cell lymphoma 2 (Bcl-2). Histology images showed CUS induced profound damage to the cerebral cortex as demonstrated by severe neuronal damage with shrunken cells, disrupted atrophic nuclei, perineuronal vacuolation and swollen glial cells. CUS also significantly (p<0.05) induced iNOS, MDA, and caspase-3, whereas SOD and Bcl-2 brain tissue levels were inhibited by CUS. In addition, data from the depression-like behavior, forced swimming test showed significant (p<0.05) increase in animal immobility and decrease in climbing ability in the model group of rats. Thus, here we demonstrated a reliable rat model of chronic stress-induced brain injury, which can further be used to investigate beneficial drugs or agents used for a period of three weeks to protect against CUS-induced brain damage.

RESUMEN: El estrés crónico es un factor de riesgo para el deterioro de la memoria y las anomalías neurológicas tanto en humanos como en animales. Intentamos investigar el alcance de lesión del tejido cerebral; (ii) estrés nitrosativo y oxidativo en homogeneizados de tejido cerebral; (iii) biomarcadores apoptóticos y de supervivencia en homogeneizados de tejido cerebral; y (iv) inmovilidad y habilidades de escalada, inducidas durante un período de tres semanas por estrés crónico impredecible (ECI). Se dejaron sin tratamiento (grupo control) ratas Wistar, o se expusieron a una variedad de factores estresantes impredecibles diariamente antes de ser sacrificadas después de 3 semanas (grupo modelo). Se realizó una evaluación del comportamiento similar a la depresión y luego se sacrificaron los animales y se tiñeron los tejidos cerebrales con tinción histológica básica y se examinaron con microscopía óptica. Además, se prepararon homogeneizados de tejido cerebral y se analizaron los siguientes parámetros; óxido nítrico sintasa inducible (iNOS), malondialdehído (MDA), superóxido dismutasa (SOD), caspasa- 3 y linfoma de células B 2 (Bcl-2). Las imágenes histológicas mostraron que el CUS indujo un daño profundo en la corteza cerebral como lo demuestra el daño neuronal severo con células encogidas, núcleos atróficos alterados, vacuolación perineuronal y células gliales inflamadas. ECI también indujo significativamente (p <0,05) iNOS, MDA y caspase-3, mientras que los niveles de tejido cerebral SOD y Bcl-2 fueron inhibidos por ECI. Además, los datos del comportamiento similar a la de- presión, la prueba de natación forzada mostró un aumento significativo (p <0,05) en la inmovilidad animal y una disminución en la capacidad de escalada en el grupo modelo de ratas. Por lo tanto, aquí demostramos un modelo confiable de daño cerebral crónico en rata inducido por el estrés, que se puede utilizar para investigar medicamentos o agentes beneficiosos usados durante un período de tres semanas para proteger el daño cerebral inducido por ECI.

Evaluating clinical and laboratory effects of ozone in non-surgical periodontal treatment: a randomized controlled trial

Abstract Objective: This study aims to evaluate the clinical and biochemical (oxidative stress and pro-inflammatory mediators) effects of the gaseous ozone use accompanied by scaling and root planning (SRP) in periodontal treatment. Material and Methods: The study population consisted of 40 patients with chronic periodontitis (CP) randomly sorted into two groups of 20. The experimental group received SRP plus 3 watts gaseous ozone in two separate applications five days apart, whereas the control group received SRP plus placebo. Clinical periodontal parameters were assayed and saliva samples were taken before the initial and one month after the second treatment. Periodontal examination assessed plaque index (PI), gingival index (GI), probing depth, and clinical attachment level (CAL). Total antioxidant status (TAS), total oxidant status (TOS), nitric oxide (NO), 8-hydroxy-2'-deoxyguanosine (8-OHdG), myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), and transforming growth factor-beta (TGF-β) levels were evaluated from saliva samples. Results: Changes following treatment in PI, GI, probing depth, and CAL scores were similar for both groups (p>0.05). Of note, TGF-β levels were observed to be higher in the treatment group than in controls (p<0.05). Changes in 8-OHdG, TAS, TOS, NO, MPO, GSH and MDA levels, however, were not significantly different between groups (p>0.05). Conclusion: The findings of this study indicate that SRP plus gaseous ozone versus SRP alone does not correlate to a significant improvement in periodontal recovery.

Associação entre níveis de ferritina e peroxidação lipídica em pacientes em hemodiálise / Association between serum ferritin and lipid peroxidation in hemodialysis patients

Resumo Introdução: A suplementação de ferro é uma das importantes recomendações em pacientes com doença renal crônica (DRC), contudo, uma sobrecarga desse mineral pode contribuir para o estresse oxidativo, condição essa bastante relacionada com o risco cardiovascular nesses pacientes. Objetivo: O objetivo desse trabalho foi investigar se os níveis de ferritina estão associados ao estresse oxidativo avaliado pelo malondialdeído (MDA) em pacientes em hemodiálise (HD). Métodos: Vinte pacientes em tratamento de HD (55,0 ± 15,2 anos, tempo de diálise de 76,5 ± 46,3 meses, IMC 23,6 ± 3,0 kg/m2) foram comparados com 11 indivíduos saudáveis (50,9 ± 8,0 anos, IMC 23,8 ± 1,9 kg/m2). O nível de MDA foi medido pela reação com o ácido tiobarbitúrico e os dados bioquímicos de rotina foram obtidos por meio do prontuário médico. Resultados: Os pacientes em HD apresentaram elevados níveis de MDA (13,2 ± 5,3 nmol/mL) quando comparados aos indivíduos saudáveis (5,1 ± 2,7 nmol/mL; p < 0,01). Doze pacientes (60%) apresentaram valores de ferritina superiores a 500 ng/mL e houve correlação positiva entre ferritina e MDA nos pacientes HD (r = 0,66; p = 0,005; n = 17). Conclusão: O excesso dos estoques de ferro em pacientes em HD resulta em um aumento da peroxidação lipídica e, consequentemente, contribui para um maior estresse oxidativo nesses pacientes. .

Abstract Introduction: Iron supplementation is one of the recommendations found in patients with chronic kidney disease (CKD), however, an overload of this mineral can contribute to oxidative stress, a condition closely related to the cardiovascular risk in these patients, as well as disease progression. Objective: The objective of this study was to investigate whether ferritin levels are associated with oxidative stress marker MDA in patients on hemodialysis (HD). Methods: Twenty HD patients (55.0 ± 15.2 years, time of dialysis 76.5 ± 46.3 months, BMI 23.6 ± 3.0 kg/m2) were compared with 11 healthy subjects (50.9 ± 8.0 years, BMI 23.8 ± 1.9 kg/m2). Malondialdehyde (MDA) was measured by reaction with thiobarbituric acid and routine biochemical data were obtained from medical records. Results: MDA levels were significantly higher in HD patients compared to the control group (13.2 ± 5.3 nmol/mL vs. 5.1 ± 2.7nmol/mL, p < 0.01). Twelve patients (60%) had ferritin values greater than the 500 ng/mL and there was a positive correlation between ferritin and MDA in HD (r = 0.66, p = 0.005, n = 17) patients. Conclusion: The excess iron stores in HD patients results in increased lipid peroxidation, and consequently contributes to increased oxidative stress in these patients. .

Oxidative stress and plasma lipoproteins in cancer patients / Estresse oxidativo e lipoproteínas plasmáticas em pacientes com câncer

Objective To evaluate the relation between oxidative stress and lipid profile in patients with different types of cancer. Methods This was an observational cross-sectional. A total of 58 subjects were evaluated, 33 males, divided into two groups of 29 patients each: Group 1, patients with cancer of the digestive tract and accessory organs; Group 2 patients with other types of cancers, all admitted to a public hospital. The plasma levels (lipoproteins and total cholesterol, HDL, and triglycerides, for example) were analyzed by enzymatic kits, and oxidative stress based on thiobarbituric acid-reactive substances, by assessing the formation of malondialdehyde. Results In general the levels of malondialdehyde of patients were high (5.00μM) as compared to 3.31μM for healthy individuals. The median values of lipids exhibited normal triacylglycerol (138.78±89.88mg/dL), desirable total cholesterol values (163.04±172.38mg/dL), borderline high LDL (151.30±178.25mg/dL) and low HDL (31.70±22.74mg/dL). Median HDL levels in Group 1 were lower (31.32mg/dL) than the cancer patients in Group 2 (43.67mg/dL) (p=0.038). Group 1 also showed higher levels of oxidative stress (p=0.027). Conclusion The lipid profile of patients with cancer was not favorable, which seems to have contributed to higher lipid peroxidation rate, generating a significant oxidative stress. .

Objetivo Avaliar a relação entre estresse oxidativo e perfil lipídico em pacientes com diferentes tipos de câncer. Métodos Estudo do tipo observacional transversal. Foram avaliados 58 indivíduos, sendo 33 do sexo masculino, divididos em dois grupos de 29 pacientes cada: o Grupo 1 foi formado por pacientes com câncer do trato digestivo e órgãos anexos; o Grupo 2 foi formado por pacientes com outros tipos de câncer, todos internados em um hospital público. Foram analisadas concentrações plasmáticas (colesterol total, HDL e triacilglicerol, entre outras), por meio de kits enzimáticos, e o estresse oxidativo, com base em substâncias reativas ao ácido tiobarbitúrico, por meio da formação de malondialdeído. Resultados Na mediana, os pacientes apresentaram valores altos de malondialdeído (5,00μM) quando comparados ao valor de 3,31μM para indivíduos saudáveis. A mediana do perfil lipídico exibiu valores de triacilgliceróis normais (138,78±89,88mg/dL), colesterol total com valores desejáveis (163,04±172,38mg/dL), LDL com limiar elevado (151,30±178,25mg/dL) e HDL baixo (31,70±22,74mg/dL). Os níveis medianos de HDL do Grupo 1 foram mais baixos (31,32mg/dL) do que dos pacientes oncológicos do Grupo 2 (43,67mg/dL) (p=0,038). O Grupo 1 apresentou níveis mais altos de estresse oxidativo (p=0,027). Conclusão O perfil lipídico de pacientes com câncer apresentou-se desfavorável, o que parece ter contribuído para uma maior taxa de peroxidação lipídica, gerando um significativo estresse oxidativo. .