Nuclear Factor Erythroid 2-Related Factor (NRF2), Heme Oxygenase 1 (HO-1) and Total Oxidant-Antioxidant Status in Patients with COVID-19 / Factor nuclear relacionado con el eritroide 2 (NRF2), hemo oxigenasa 1 (HO-1) y estado oxidante-antoxidante total en pacientes con COVID-19

Introduction: Studies on nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) levels in COVID-19 patients are limited. This study aimed to investigate the relationship between some biomarkers of oxidant-antioxidant status with COVID-19 disease. Material and methods: The patients older than 18 years of age who tested positive for SARS CoV-2 PCR (polymerase chain reaction) with clinical symptoms and signs were included in this study. Total antioxidant status (TAS), total antioxidant status (TOS), oxidative stress index (OSI) and HO-1 and Nrf2 levels were analyzed from serum samples taken before and after treatment. Results: In this study, 16 patients followed up with the diagnosis of COVID-19 were included. 9 (56.3%) of the patients were female and 7 (43.8%) were male. The mean age was 33.75 ± 17.03 years. All patients were symptomatic and were hospitalized to be followed up. It was determined that Nrf2 and HO-1 values increased significantly after treatment. Moreover, there was a significant positive correlation between Nrf2 and TAS values and TAS increases significantly in parallel to an increase in Nrf2, and there was a significant but negative correlation between Nrf2 and TOS and OSI values, and thus an increase in Nrf2 led to a decrease in TOS and OSI values. There was a significant positive correlation between HO-1 and TAS, and TAS increased significantly, as HO-1 increased. Conclusions: The decrease in TOS and OSI and the increase in Nrf2 and HO-1 during the follow-up period in COVID-19 patients suggest that the body tries to prevent ROS-related oxidative stress via Nrf2 and HO-1 and that oxidative stress may have a key role in the pathophysiology of COVID-19. (AU)

Introducción: Los estudios sobre los niveles del factor 2 relacionado con el factor nuclear eritroide 2 (Nrf2) y la hemo oxigenasa-1 (HO-1) en pacientes con COVID-19 son limitados. Este estudio tuvo como objetivo investigar la relación entre algunos biomarcadores del estado oxidante-antioxidante con la enfermedad COVID-19. Material y métodos: Se incluyeron en este estudio los pacientes mayores de 18 años que dieron positivo a PCR (reacción en cadena de la polimerasa) de SARS CoV-2 con síntomas y signos clínicos. Se analizaron el estado antioxidante total (TAS), el estado antioxidante total (TOS), el índice de estrés oxidativo (OSI) y los niveles de HO-1 y Nrf2 a partir de muestras de suero tomadas antes y después del tratamiento. Resultados: En este estudio se incluyeron 16 pacientes seguidos con diagnóstico de COVID-19. 9 (56,3%) de los pacientes eran mujeres y 7 (43,8%) eran hombres. La edad media fue 33,75 ± 17,03 años. Todos los pacientes presentaban síntomas y fueron hospitalizados para seguimiento. Se determinó que los valores de Nrf2 y HO-1 aumentaron significativamente después del tratamiento. Además, hubo una correlación positiva significativa entre los valores de Nrf2 y TAS y TAS aumenta significativamente en paralelo a un aumento en Nrf2, y también hubo una correlación significativa pero negativa entre Nrf2 y los valores de TOS y OSI y, por lo tanto, un aumento en Nrf2 condujo a una disminución en los valores TOS y OSI. Hubo una correlación positiva significativa entre HO-1 y TAS, y TAS aumentó significativamente a medida que aumentaba HO-1. Conclusiones: La disminución de TOS y OSI y el aumento de Nrf2 y HO-1 durante el período de seguimiento en pacientes con COVID-19 sugieren que el cuerpo intenta prevenir el estrés oxidativo relacionado con ROS a través de Nrf2 y HO-1 y que el estrés oxidativo puede tener un papel clave en la fisiopatología de COVID-19. (AU)

The relationship between thiol-disulfide balance and idiopathic sudden sensorineural hearing loss / Relação entre equilíbrio tiol-dissulfeto e perda auditiva neurossensorial súbita idiopática

Abstract Introduction: Impaired cochlear perfusion is a major etiological factor in idiopathic sudden sensorineural hearing loss. Oxidative stress has been shown to be a risk factor for oxidative damage. Objectives: We investigated the role of oxidative stress in idiopathic sudden sensorineural hearing loss by comparing serum levels of oxidant and antioxidant molecules including thiol/disulfide homeostasis paraoxonase, stimulated thiol/disulfide homeostasis paraoxonase, arylesterase, ceruloplasmin and myeloperoxidase in patients who did and did not recover after treatment. Methods: The amount of dynamic disulfide was calculated by determining half of the difference between the total thiols and native thiols. After the determination of native, total thiol, and disulfide amounts, the disulfide/total thiol percent ratio, native thiol/total thiol ratio and disulfide/native thiol percent ratio were calculated and then compared between the two groups. Additionally, clinical relationship between audiological recovery and native thiol, disulfide, disulfide/native thiol percent ratio, and disulfide/total thiol percent ratio levels was investigated. Blood samples were also analyzed for the assessment of thiol/disulfide homeostasis paraoxonase, stimulated thiol/disulfide homeostasis paraoxonase, arylesterase, ceruloplasmin, and myeloperoxidase levels. Results: A significant difference was found between the two groups with regard to total oxidant status disulfide, disulfide/native thiol percent ratio, disulfide/total thiol percent ratio, and native thiol/total thiol ratio levels (p = 0.001, p = 0.001, p = 0.001, p = 0.003, p = 0.001, p = 0.002, respectively). However, no significant difference was found between the two groups with regard to thiol/disulfide homeostasis paraoxonase, stimulated thiol/disulfide homeostasis paraoxonase, ceruloplasmin, and myeloperoxidase levels (p > 0.05 for all). Conclusion: The results supported the common hypothesis that vascular pathologies are the primary cause of idiopathic sudden sensorineural hearing loss and that other etiological factors ultimately result in vascular pathologies. The oxidant-antioxidant and thiol-disulfide balances were impaired in the idiopathic sudden sensorineural hearing loss group.

Resumo Introdução: A perfusão coclear prejudicada é um fator etiológico importante na perda auditiva neurossensorial súbita idiopática (PANSSI). O estresse oxidativo mostrou ser um fator de risco para danos oxidativos. Objetivos: Investigamos o papel do estresse oxidativo na PANSSI mediante a comparação dos níveis séricos de moléculas oxidantes e antioxidantes, inclusive homeostase de tiol/dissulfeto, paraoxonase, paraoxonase estimulada, arilesterase, ceruloplasmina e mieloperoxidase em pacientes com e sem recuperação após o tratamento. Método: A quantidade de dissulfeto dinâmico foi calculada mediante a determinação de metade da diferença entre os tiois totais e os tiois nativos. Após a determinação das quantidades de tiol nativo, tiol total e dissulfeto, as razões percentuais de dissulfeto/tiol total, tiol nativo/tioltotal e dissulfeto/tiol nativo foram calculadas e depois comparadas entre os dois grupos. Além disso, a relação clínica entre a recuperação audiológica e os níveis de tiol nativo, tiol nativo/tiol total, dissulfeto, dissulfeto/tiol nativo e dissulfeto/tiol total foi investigada. Amostras de sangue também foram analisadas para avaliar os níveis de paraoxonase, paraoxonase estimulada, arilesterase, ceruloplasmina e mieloperoxidase. Resultados: Uma diferença significante foi encontrada entre os dois grupos em relação ao estado oxidante total e aos níveis de dissulfeto, dissulfeto/tiol nativo, dissulfeto/tiol total, tiol nativo/tiol total (p = 0,001, p = 0,001, p = 0,001, p = 0,003, p = 0,001, p = 0,002, respectivamente). Porém, não foi encontrada diferença significante entre os dois grupos em relação aos níveis de paraoxonase, paraoxonase estimulada, ceruloplasmina e mieloperoxidade (p> 0,05 para todos). Conclusão: Os resultados apoiaram a hipótese comum de que as doenças vasculares são a principal causa de PANSSI e que, em última análise, outros fatores etiológicos resultam em doenças vasculares. Os equilíbrios de oxidante-antioxidante e tiol-dissulfeto estavam prejudicados no grupo PANSSI.

Relationships between paroxysmal atrial fibrillation, total oxidant status, and DNA damage.

INTRODUCTION: Structural and electrophysiological changes play a critical role in the development of atrial fibrillation (AF). Although the pathophysiology of paroxysmal AF (PAF) has not been fully elucidated, oxidative stress (OS) and DNA damage appear to be important triggers. Thus far, no studies have investigated the relationships among total oxidant status (TOS), DNA damage, and PAF. The goal of this study was to assess TOS and DNA damage in patients with PAF. METHODS: This cross-sectional study included 56 patients with PAF and 31 healthy controls. OS was assessed based on TOS, total antioxidant capacity (TAC), and oxidative stress index (OSI). The level of DNA damage was assessed using 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: There were no significant differences between the groups in terms of baseline characteristics. However, patients with PAF had significantly higher high-sensitivity C-reactive protein (p=0.018), TOS (p=0.001), OSI (p=0.001), and 8-OHdG (p=0.019) levels, compared with the control group. Multivariate logistic regression analysis showed that serum TOS level (odds ratio: 1.608; 95% confidence interval [CI]: 1.188-2.176, p=0.002) was the only independent predictor of PAF. TOS ≥12.2 predicted PAF with a sensitivity of 82% and specificity of 76% (AUC: 0.785, 95% CI: 0.687-0.883, p<0.001). CONCLUSION: We found that TOS and DNA damage were significantly greater in patients with PAF than in the control group. Therefore, we propose that TOS and DNA damage can be used to detect patients at higher risk of AF.

Perfil bioquímico nutricional en un grupo de pacientes con cáncer de cabeza y cuello / Nutritional biochemical profile in a group of patients with head and neck cancer / Perfil bioquímico nutricional num grupo de pacientes com câncer de cabeça e pescoço

El objetivo del trabajo fue evaluar el estado nutricional mediante diferentes parámetros bioquímicos en 17 pacientes adultos de ambos sexos, con cáncer de cabeza y cuello, seleccionados y asistidos en el Instituto Oncológico A. Roffo al inicio del tratamiento. Las muestras de sangre fueron recolectadas en ayunas y sobre el suero separado por centrifugación se determinaron las siguientes fracciones proteicas: transtiretina (TTR), transferrina (Transf), fracciones de complemento C3 y C4 (C3c, C4c), ceruloplasmina (Cp), haptoglobina (Hp), proteína C reactiva (PCR), por inmunodifusión radial cuantitativa en placas (Binding Site, Reino Unido; Diffu-Plate, Biocientífica SA, Argentina); la concentración de IL-4 fue determinada por el método de Elisa y se evaluó el estado antioxidante total (TAS) (Kit RANDOX, Reino Unido). Sobre el 58% de los pacientes (n=10) se analizó el perfil de ácidos grasos por cromatografía gaseosa. Los ácidos oleico, linoleico, araquidónico (AA), α-linolénico, eicosapentaenoico (EPA) y docosahexaenoico (DHA) fueron identificados por el tiempo de retención y calculados como porcentaje del total de los ácidos grasos. Los resultados fueron expresados como X±DE y comparados con valores obtenidos en individuos sanos (VR). Los resultados muestran una disminución en los niveles séricos de TTR, C3c, Transf, e IL4 con aumento concomitante de Cp y Hp con respecto a los VR; estos resultados indican un comprometido estado nutricional e inflamatorio. También se observa un estado antioxidante total deprimido y disminución en la concentración de ácidos grasos esenciales (ω3 y ω6). El análisis global de estos hallazgos demuestra la importancia de la evaluación nutricional temprana y periódica de estos pacientes; esto permitiría realizar una valoración precoz de la necesidad de un apropiado tratamiento nutricional específico.

The aim of the study was to evaluate the nutritional status of 17 patients suffering from head and neck cancer, who attended Angel Roffo Institute of Oncology, at the beginning of the specific treatment, through the use of biochemical parameters. Blood samples were collected from fasting patients. Specific serum protein fractions transthyretin (TTR), transferrin (Transf), C3 and C4 complement fractions (C3c,C4c); ceruloplasmin (Cp), haptoglobin (Hp) and C-reactive protein (RCP) were measured by single radial immunodiffusion technique on agar gel layers (Binding Site, UK; Diffu-Plate, Biocientífica SA, Argentina). The level of IL-4 was determined by Elisa method and total antioxidant status (TAS) by Randox Kit (UK). On 58% of patients (n=10) the fatty acid profile was analyzed. Results expressed as X±SD were compared with reference values performed in a group of healthy individuals. Data showed lower TTR, C3c, Transferrin and IL-4 together with higher Cp and Haptoglobin sera levels than reference values. The results pointed out to a depressed nutritional status and inflammation. Also, diminishment in the total antioxidant status and in essential fatty acids ω3 and ω6 was observed. These findings showed the importance of an early and periodic nutritional evaluation that could help to perform an adequate nutritional support concomitant with the specific treatment.

O objetivo do trabalho foi avaliar o estado nutricional através de diferentes parâmetros bioquímicos em 17 pacientes adultos de ambos os sexos, com câncer de cabeça e pescoço, selecionados e assistidos, no Instituto Oncológico A. Roffo, no início do tratamento. As amostras de sangue foram coletadas em jejum e sobre o soro separado por centrifugação foram determinadas as seguintes frações proteicas: transtirretina (TTR), transferrina (Transf), frações de complemento C3 e C4 (C3c, C4c), ceruloplasmina (Cp), haptoglobina (Hp), proteína C reativa (PCR), por imunodifusão radial quantitativa em placas (Binding Site, Reino Unido; Diffu-Plate, Biocientífica SA, Argentina); a concentração de IL-4 foi determinada pelo método de Elisa e se avaliou o estado antioxidante total (TAS) (Kit RANDOX, Reino Unido). Sobre 58% dos pacientes (n=10) foi analisado o perfil de ácidos graxos por cromatografia gasosa. Os ácidos oleico, linoleico, araquidônico (AA), α-linolênico, eicosapentaenoico (EPA) e docosahexaenoico (DHA) foram identificados pelo tempo de retenção e calculados como percentual do total dos ácidos graxos. Os resultados foram expressos como X±DE e comparados com valores obtidos em indivíduos saudáveis (VR). Os resultados mostram uma diminuição nos níveis séricos de TTR, C3c, Transf, e IL4 com aumento concomitante de Cp e Hp com relação aos VR; estes resultados indicam um comprometido estado nutricional e inflamatório. Também se observa um estado antioxidante total deprimido e diminuição na concentração de ácidos graxos essenciais (ω3 e ω6). A análise global destes achados demonstra a importância da avaliação nutricional precoce e periódica destes pacientes; isto permitiria realizar uma avaliação precoce da necessidade de um adequado tratamento nutricional específico.