Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To evaluate the effects of ezetimibe/simvastatin (EZE/SIMV) and rosuvastatin (ROSUV) on oxidative stress (OS) markers in patients with diabetic polyneuropathy (DPN). METHODS: We performed a randomized, double-blind, placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus (T2DM) and DPN, as evaluated by composite scores and nerve conduction studies (NCS). Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo, EZE/SIMV 10/20 mg, or ROSUV 20 mg for 16 weeks. All patients were assessed before and after treatment: primary outcomes were lipid peroxidation (LPO), and nitric oxide (NO) surrogate levels in plasma; secondary outcomes included NCS, neuropathic symptom scores, and metabolic parameters. Data were expressed as mean ± SD or SEM, frequencies, and percentages; we used nonparametric analysis. RESULTS: LPO levels were reduced in both statin arms after 16 weeks of treatment (p < 0.05 versus baseline), without changes in the placebo group. NO levels were not significantly affected by statin treatment, although a trend towards significance concerning increased NO levels was noted in both statin arms. No significant changes were observed for the NCS or composite scores. DISCUSSION: EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy. This trial is registered with NCT02129231.

Effect of necrosectomy and vacuum-assisted closure (VAC) on mitochondrial function and oxidative stress markers in severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is associated with high morbidity and mortality. OBJECTIVE: To evaluate whether necrosectomy, alone or combined with vacuum-assisted closure (VAC), has any additional beneficial effects on mitochondrial function and/or oxidative stress markers in SAP. METHODS: Patients with SAP, APACHE II score > 8, and inadequate response to management in an intensive care unit were included in a prospective observational study. Sixteen underwent necrosectomy and 24 underwent necrosectomy plus VAC every 48 h. Patients were then categorized as survivors or deceased. Submitochondrial membrane fluidity of platelets and F0F1-ATPase hydrolysis were measured to represent mitochondrial function. Oxidative/nitrosative stress was measured using lipoperoxides (LPOs), nitric oxide (NO), erythrocyte membrane fluidity, and total antioxidant capacity (TAC). RESULTS: Membrane fluidity in submitochondrial particles of platelets remained significantly increased throughout the study, and then eventually rised in deceased patients managed with necrosectomy + VAC vs. survivors (p < 0.041). Hydrolysis was significantly increased from baseline to endpoint in all patients, predominating in those who died after management with necrosectomy (p < 0.03). LPO increased in all patients, and necrosectomy was more efficient for the eventual decrease in survivors (p < 0.039). NO was found to be increased for the baseline-endpoint result among both survivors and deceased patients with both management options. Erythrocyte membrane fluidity was increased in survivors managed with necrosectomy + VAC, and eventually returned to normal (p < 0.045). TAC was found to be consumed in all patients for the duration of the study. CONCLUSIONS: Mitochondrial dysfunction and oxidative/ nitrosative stress with significant systemic antioxidant consumption were found. Necrosectomy was more efficient and better cleared LPOs. Necrosectomy + VAC improved erythrocyte membrane fluidity and increased survival.

Efecto de la necrosectomía y el sistema de cierre asistido al vacío (VAC) sobre función mitocondrial y marcadores de estrés oxidativo en pancreatitis aguda severa / Effect of necrosectomy and vacuum-assisted closure (VAC) on mitochondrial function and oxidative stress markers in severe acute pancreatitis

Antecedentes: la pancreatitis aguda severa (PAS) se asocia con alta morbilidad y mortalidad. Objetivo: evaluar si la necrosectomía sola o necrosectomía + el sistema de cierre al vacío (VAC), ofrece efectos favorables adicionales en la función mitocondrial y/o marcadores de estrés oxidativo en PAS. Métodos: mediante un estudio observacional prospectivo, se incluyeron pacientes con PAS y APACHE II > 8 sin respuesta satisfactoria al manejo en la Unidad de Cuidados Intensivos. Dieciséis pacientes se sometieron a necrosectomía y 24 a necrosectomía + VAC cada 48 h. Se dividieron en sobrevivientes y fallecidos. Se determinó la fluidez de la membrana submitocondrial de las plaquetas y la hidrólisis de la F0F1-ATPasa como función mitocondrial. El estrés oxidativo/nitrosativo se midió mediante lipoperóxidos (LPO), óxido nítrico (ON), fluidez de la membrana de eritrocitos y capacidad antioxidante total (CAT). Resultados: la fluidez de membrana de partículas submitocondriales de plaquetas se mantuvo incrementada significativamente durante todo el estudio y aumentó al final en los fallecidos tratados con necrosectomía + VAC vs. los sobrevivientes (p < 0,041). La hidrólisis se encontró significativamente elevada desde el inicio hasta el final en todos los pacientes, predominando en los que fallecieron tratados con necrosectomía (p < 0,03). Hubo aumento de LPO en todos los pacientes aunque la necrosectomía fue más eficaz en la disminución al final en sobrevivientes (p < 0,039). El ON se encontró incrementado durante el resultado basal-final en sobrevivientes y fallecidos en ambas alternativas de tratamiento. La fluidez de la membrana de eritrocitos se encontró incrementada en los sobrevivientes tratados con necrosectomía + VAC y se normalizó al final (p < 0,045). La CAT se encontró consumida en todos los pacientes durante todo el estudio. Conclusiones: se encontró disfunción mitocondrial y estrés oxidativo/nitrosativo con consumo importante de los antioxidantes sistémicos. La necrosectomía fue más eficiente al eliminar mejor los LPO. La necrosectomía + VAC mejoró la fluidez de la membrana de eritrocitos e incrementó la sobrevida (AU)

Background: Severe acute pancreatitis (SAP) is associated with high morbidity and mortality. Objective: To evaluate whether necrosectomy, alone or combined with vacuum-assisted closure (VAC), has any additional beneficial effects on mitochondrial function and/or oxidative stress markers in SAP. Methods: Patients with SAP, APACHE II score > 8, and inadequate response to management in an intensive care unit were included in a prospective observational study. Sixteen underwent necrosectomy and 24 underwent necrosectomy plus VAC every 48 h. Patients were then categorized as survivors or deceased. Submitochondrial membrane fluidity of platelets and F0F1-ATPase hydrolysis were measured to represent mitochondrial function. Oxidative/nitrosative stress was measured using lipoperoxides (LPOs), nitric oxide (NO), erythrocyte membrane fluidity, and total antioxidant capacity (TAC). Results: Membrane fluidity in submitochondrial particles of platelets remained significantly increased throughout the study, and then eventually rised in deceased patients managed with necrosectomy + VAC vs. survivors (p < 0.041). Hydrolysis was significantly increased from baseline to endpoint in all patients, predominating in those who died after management with necrosectomy (p < 0.03). LPO increased in all patients, and necrosectomy was more efficient for the eventual decrease in survivors (p < 0.039). NO was found to be increased for the baseline-endpoint result among both survivors and deceased patients with both management options. Erythrocyte membrane fluidity was increased in survivors managed with necrosectomy + VAC, and eventually returned to normal (p < 0.045). TAC was found to be consumed in all patients for the duration of the study. Conclusions: Mitochondrial dysfunction and oxidative/ nitrosative stress with significant systemic antioxidant consumption were found. Necrosectomy was more efficient and better cleared LPOs. Necrosectomy + VAC improved erythrocyte membrane fluidity and increased survival (AU)