Niveles glutatión reducido y estado redox celular en pacientes pediátricos con inmunodeficiencias / Reduced glutathione levels and cellular redox status in pediatric patients with immunodeficiencies

Introducción: Las alteraciones en el estado redox celular se han descrito como factores causales en diversas enfermedades. La depleción del glutatión reducido se ha asociado fundamentalmente a enfermedades neurodegenerativas, pulmonares, hepáticas, cardiovasculares e inmunológicas. Objetivo: Determinar las concentraciones de glutatión reducido y el estado redox celular en pacientes pediátricos con inmunodeficiencias. Métodos: Se estudiaron 21 pacientes con inmunodeficiencias procedentes de la consulta de Inmunogenética, en edades comprendidas entre 1 y 8 años, de ambos sexos, y 8 niños en el mismo rango de edad de los pacientes, como grupo control, con estudios de inmunidad humoral y celular normales. Los pacientes con diagnóstico de inmunodeficiencia se dividieron para su estudio en 2 grupos según el componente afectado de la respuesta inmune: humoral y celular. Fueron determinadas las concentraciones intraeritrocitarias de glutatión reducido y oxidado, mediante un método de HPLC-UV. Para evaluar el estado redox celular se calculó la relación entre las formas reducidas y oxidadas del glutatión (GSH/GSSG). Resultados: Las concentraciones de glutatión reducido y el estado redox celular se encontraron disminuidos en ambos grupos de pacientes en relación con los niños sin inmunodeficiencia (p=0,031 y p=0,03; respectivamente). El glutatión oxidado no mostró diferencias entre los grupos. Conclusiones: En los pacientes con inmunodeficiencia se evidenció la afectación del estado redox celular como consecuencia de la disminución del glutatión reducido. Este primer acercamiento ofreció las potencialidades del empleo de estos biomarcadores en la evaluación integral de pacientes con inmunodeficiencia(AU)

Introduction: Alterations in the cellular redox state have been described as causal factors in various diseases. Reduced glutathione depletion has been fundamentally associated with neurodegenerative, pulmonary, liver, cardiovascular and immunological diseases. Objective: To determine the concentrations of reduced glutathione and the cellular redox status in pediatric patients with immunodeficiencies. Methods: We studied 21 patients with immunodeficiencies from the immunogenetic service, aged between 1 and 8 years and as a control group, 8 children in the same age range as the patients, with normal humoral and cellular immunity studies. Patients diagnosed with immunodeficiency were divided into two groups according to the affected component of the immune response: humoral and cellular. The intraerythrocyte concentrations of oxidized and reduced glutathione were determined by means of an HPLC-UV method. To evaluate the cellular redox state, the relationship between the reduced and oxidized forms of glutathione (GSH/GSSG) was calculated. Results: Reduced glutathione concentrations and cellular redox status were found to be decreased in both groups of patients in relation to children without immunodeficiency (p=0,031 and p=0,03; respectively). Oxidized glutathione showed no difference between the groups. Conclusions: In patients with immunodeficiency, the cellular redox state is affected as a consequence of the decrease in reduced glutathione. This first approach offers the potential for the use of these biomarkers in the comprehensive evaluation of patients with immunodeficiency(AU)

Glutathione: Glutathione Sulfide Redox Imbalance in Early Impaired Fasting Glucose.

Aim: The current study aims to examine the balance between glutathione and glutathione sulfide and how this was disturbed in patients with impaired fasting glucose (IFG) level. The study also included 8-hydroxy-2’-deoxyguanosine to provide a more comprehensive picture of the overall redox state. Methodology: A cross-sectional analysis of ninety medication free participants without reported history of cardiovascular disease and/or diabetes mellitus was undertaken with data collected from the Diabetes Complications Research Initiative database at Charles Sturt University. Fasting blood glucose, HbA1c and cholesterol as standard markers for diabetes mellitus and associated complications were measured in addition to the emerging biomarkers glutathione (GSH), glutathione disulfide (GSSG), and urinary 8- hydroxy-2’-deoxyguanosine (8OHdG). Results: The IFG group had a mean blood glucose level above 6.1mmol/L being significantly higher compared to control (P<0.001). Traditional clinical markers were all within the normal range for both groups. However the GSH/GSSG ratio (8.53±5.4 vs 6.62±2.2, P=.04) was significantly lower in the IFG group. GSH and 8OHdG, being markers for oxidative stress, were not significantly different between the two groups. Conclusion: The free radical related changes in metabolic redox pathways are linked to oxidative stress and related pathologies but may not be associated with disease progression, providing an explanation why conflicting results are presented in the literature concerning any individual biomarkers and risk of diabetes. Our study included individuals with no medication use and mild hyperglycemia (impaired fasting glucose) and indicates a pro-oxidant response to mild-moderate hyperglycemia with a moderate rise in oxidative DNA damage.