Efecto citotóxico de annona muricata en modelos preclínicos experimentales de cáncer

El cáncer es la tercera causa de muerte en nuestro país después de las enfermedades cardiacas y diabetes mellitus. Existen diversos tratamientos para este padecimiento (antimetabolitos, agentes alquilantes, antibióticos, inhibidores de la mitosis, etc.) que se han empleado sin obtener resultados positivos en la mayoría de los casos. De ahí surge la búsqueda de nuevas alternativas terapéuticas etnofarmacológicas aún más específicas. La Annona muricata mejor conocida como guanábana es una planta que ha mostrado poseer compuestos con efecto citotóxico en modelos in vitro de adenocarcinoma prostático, carcinoma pancreático, cáncer de colon, hígado y pulmón. El presente trabajo tiene como objetivo evaluar la información bibliográfica-científica disponible en las bases de datos para determinar la factibilidad de utilizar A. muricata como agente citotóxico en fase preclínica y clínica de cáncer. Se realizó una revisión bibliografía-científica en bases de datos (BVS, EBSCO, PubMed, SciELO y SeCiMed) con las palabras clave Anonna muricata y cáncer. Se encontraron artículos de trabajos científicos que se enfocan en estudios in vitro, en el cual, se observó un efecto citotóxico significativo principalmente en líneas celulares de cáncer de hígado, páncreas y pulmón. Se reportan compuestos como las acetogeninas y annopentocinas que han mostrado efecto citotóxico parecido o superior a fármacos usados en la quimioterapia. A. muricata muestra efecto citotóxico significativo en las revisiones bibliográficas, principalmente en líneas celulares cancerosas (estudios in vitro), pero aún faltan estudios a nivel preclínico que evalúen no solo el efecto citotóxico, si no también la evaluación de bioseguridad en un organismo vivo y posteriores estudios a nivel clínico. El bajo número de evidencia no recomienda el uso de ningún extracto o principio activo de A. muricata en uso clínico

Vascular Calcification and Oxidative DNA Damage as Nontraditional Cardiovascular Risk Factors in Chronic Renal Disease

The number of CKD sufferers that require renal replacement techniques (RRTs) is increasing. The severity of cardiovascular disease (CVD) is disproportionate in these kinds of patients and contributes considerably to mortality in CKD patients. We evaluated the association between oxidative DNA damage, antioxidant activity and vascular calcification (VC) in CKD. An analytical cross-sectional study was performed. Two simple plaques were taken for each patient (pelvis-hip, and hands-wrists). The presence of VC was scored as presence (1) and absence (0). Oxidative stress was determined by activity of catalase, superoxide dismutase (SOD) and oxidative DNA damage by determination of 8-OHdG marker. Eighty-one patients were included. The RRT type was similar for hemodialysis (HD) and peritoneal dialysis (PD). Thirty-eight patients (47%) presented VC (p < 0.01); in 61%, the VC was severe (≥3 points). VC prevalence in women was significantly higher, (67%) (p < 0.001), and (29%) men. Sixty four percent of the patients submitted to HD presented VC and 27% to PD (p < 0.001). The activity of the catalase enzyme was significantly decreased in CKD vs. the healthy control (HC) (p < 0.0001). The oxidative DNA damage in CKD was greater vs. HC (p < 0.0001). In conclusion, the VC was frequent (47%) in CKD, and decreased catalase activity and greater oxidative DNA damage

Oxidative Stress, Apoptosis, and Mitochondrial Function in Diabetic Nephropathy

Diabetic nephropathy (DN) is the second most frequent and prevalent complication of diabetes mellitus (DM). The increase in the production of oxidative stress (OS) is induced by the persistent hyperglycemic state capable of producing oxidative damage to the macromolecules (lipids, carbohydrates, proteins, and nucleic acids). OS favors the production of oxidative damage to the histones of the double-chain DNA and affects expression of the DNA repairer enzyme which leads to cell death from apoptosis. The chronic hyperglycemic state unchains an increase in advanced glycation end-products (AGE) that interact through the cellular receptors to favor activation of the transcription factor NF-κB and the protein kinase C (PKC) system, leading to the appearance of inflammation, growth, and augmentation of synthesis of the extracellular matrix (ECM) in DN. The reactive oxygen species (ROS) play an important role in the pathogenesis of diabetic complications because the production of ROS increases during the persistent hyperglycemia. The primary source of the excessive production of ROS is the mitochondria with the capacity to exceed production of endogenous antioxidants. Due to the fact that the mechanisms involved in the development of DN have not been fully clarified, there are different approaches to specific therapeutic targets or adjuvant management alternatives in the control of glycemia in DN

Importancia del metabolismo y consumo de las vitaminas D y C durante la infección por SARS-CoV-2

Introduction. Since December 2019, the world has experienced a public health emergency due to the appearance of a new coronavirus, SARS-CoV-2. Epidemiological studies suggest that the capacity of the immune system modifi ed by various risk factors may be a determining factor in the prognosis of the patient, as well as an important protective eff ect has been attributed to vitamins D and C. Objective. This review aims to investigate the possible protective mechanisms of vitamins C and D as antioxidants and immunomodulators during COVID-19 disease. Methodology. A systematic search in databases such as PUBMED was used to identify clinical studies, as well as studies in animal and in vitro models that propose the mechanisms by which vitamins C and D may play an anti-infl ammatory and antioxidant role during infection with COVID-19VITAMINAS D Y C SOBRE COVID 19 Introducción. Desde diciembre de 2019 el mundo ha vivido una emergencia de salud pública debido a la aparición de un nuevo coronavirus, el SARS-CoV-2. Los estudios epidemiológicos sugieren que la capacidad del sistema inmunológico modificado por diversos factores de riesgo puede ser algo determinante en el pronóstico del paciente, así como se les ha atribuido un efecto importante como protectores a las vitaminas C y D. Objetivo. Esta revisión tiene como objetivo investigar los posibles mecanismos protectores de las vitaminas C y D como antioxidantes e inmunomodulares durante el curso de la enfermedad de COVID-19. Metodología. Se empleó una búsqueda sistemática en bases de datos como PUBMED para identificar estudios clínicos, así como estudios en modelos animales e in vitro que proponen los mecanismos por los cuales las vitaminas C y D pueden desempeñar un papel antiinflamatorio y antioxidante durante la infección con COVID-1

The Role of Oxidative Stress, Mitochondrial Function, and Autophagy in Diabetic Polyneuropathy

Diabetic polyneuropathy (DPN) is the most frequent and prevalent chronic complication of diabetes mellitus (DM). The state of persistent hyperglycemia leads to an increase in the production of cytosolic and mitochondrial reactive oxygen species (ROS) and favors deregulation of the antioxidant defenses that are capable of activating diverse metabolic pathways which trigger the presence of nitro-oxidative stress (NOS) and endoplasmic reticulum stress. Hyperglycemia provokes the appearance of micro- and macrovascular complications and favors oxidative damage to the macromolecules (lipids, carbohydrates, and proteins) with an increase in products that damage the DNA. Hyperglycemia produces mitochondrial dysfunction with deregulation between mitochondrial fission/fusion and regulatory factors. Mitochondrial fission appears early in diabetic neuropathy with the ability to facilitate mitochondrial fragmentation. Autophagy is a catabolic process induced by oxidative stress that involves the formation of vesicles by the lysosomes. Autophagy protects cells from diverse stress factors and routine deterioration. Clarification of the mechanisms involved in the appearance of complications in DM will facilitate the selection of specific therapeutic options based on the mechanisms involved in the metabolic pathways affected. Nowadays, the antioxidant agents consumed exogenously form an adjuvant therapeutic alternative in chronic degenerative metabolic diseases, such as DM

Factors Possibly Associated with Mortality in Intubated COVID-19 Patients: A Retrospective Study

In Mexico, there is a high mortality rate among patients intubated because of COVID-19. The objective of this study was to investigate the associations of age, comorbidities, and biochemical parameters with the in-hospital mortality of COVID-19 patients. A retrospective study of 79 intubated patients admitted to one hospital in Jalisco, Mexico, between July 2020 and January 2021 was performed. Demographic and clinical characteristics were collected. The mean age was 57.7 (±12.8) years, with 83.5% non-survivors and 16.5% survivors. Age, lactate dehydrogenase (LDH) and D-dimer levels were found to be significantly higher in the non-survivor group (p = 0.011, p = 0.026, p = 0.007, respectively). Patients ≥58 years had a high risk of mortality (OR = 7.017). Significant correlations were also found in some of the study variables: LDH levels and leukocyte count (r = 0.388, p = 0.034) and CRP levels and fibrinogen (r = 0.692, p ˂ 0.001) in the patients ˂58 years. Leukocyte count with LDH levels (r = 0.381, p = 0.024) were significant in the group ≥58 years. No significant difference was observed in the presence of diabetes mellitus (DM) and hypertension. In conclusion, according to logistic regression analysis, age over 58 years represents the main factor associated with mortality in these patients

Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 Supplementation on Infectious Diseases

With the appearance of new viruses and infectious diseases (ID) such as COVID-19 in 2019, as well as the lack of specific pharmacological tools for the management of patients with severe complications or comorbidities, it is important to search for adjuvant treatments that help improve the prognosis of infectious disease patients. It is also important that these treatments limit the oxidative and hyperinflammatory damage caused as a response to pathogenic agents, since, in some cases, an inflammatory syndrome may develop that worsens the patient’s prognosis. The potential benefits of complementary nutrients and dietary interventions in the treatment of pathological processes in which oxidative stress and inflammation play a fundamental role have been widely evaluated. Coenzyme Q10 (CoQ10) is a supplement that has been shown to protect cells and be effective in cardiovascular diseases and obesity. Additionally, some studies have proposed it as a possible adjuvant treatment in viral infections. Preclinical and clinical studies have shown that CoQ10 has anti-inflammatory and antioxidant effects, and effects on mitochondrial dysfunction, which have been linked to the inflammatory response

“Revisión Bibliográfica Sobre los Efectos Antineoplásicos de Annona muricata en Modelos Preclínicos de Cáncer”

Hoy en día las tres principales causas de muerte en México son las enfermedades cardiacas, la diabetes mellitus y el cáncer. Para esta última existen tratamientos antineoplásicos como antimetabolitos, agentes alquilantes, antibióticos, inhibidores de la mitosis, etc. que se han empleado sin obtener resultados positivos en la mayoría de los casos. De ahí surge la necesidad de buscar nuevas alternativas terapéuticas etnofarmacológicas como es la Annonamuricatamejor conocida como Guanábana, es una planta que ha mostrado poseer compuestos con efecto citotóxico en modelos in vitro de adenocarcinoma prostático, carcinoma pancreático, cáncer de colon, hígado y pulmón. El presente trabajo tiene como objetivo evaluar la información bibliográfica-científica disponible en las bases de datos para determinar la factibilidad de utilizar A. muricata como agente citotóxico en fase preclínica y clínica de cáncer. Se realizó una revisión bibliografía-científica en bases de datos (BioMedSearch, EBSCO, Elsevier, PubMed, SciELO y Springer) con las palabras clave Anonnamuricata y cáncer. Se encontraron artículos de trabajos científicos que se enfocan en estudios in vitro, en el cual, se observó un efecto citotóxico significativo principalmente en líneas celulares de cáncer de hígado, páncreas y pulmón. Se reportan compuestos como las acetogeninas y annopentocinas que han mostrado efecto citotóxico parecido o superior a fármacos usados en la quimioterapia. A. muricata muestra efecto citotóxico significativo en las revisiones bibliográficas, principalmente en líneas celulares cancerosas (estudios in vitro), pero aún faltan estudios a nivel preclínico que evalúen no solo el efecto citotóxico, si no, también la evaluación de bioseguridad en un organismo vivo y posteriores estudios a nivel clínico. El bajo número de evidencia no recomienda el uso de ningún extracto o principio activo de A. muricata en uso clínico

Effect of statins on oxidative DNA damage in diabetic polyneuropathy

Oxidative stress induces nerve damage in type 2 diabetes mellitus and leads to diabetic polyneuropathy (DPN) and can affect the DNA and antioxidant status. Statins have pleiotropic, protective effects on the peripheral nerves of patients with diabetes. The aim of this study was to determine the effects of ezetimibe/simvastatin and rosuvastatin on DNA damage in patients with DPN. This randomized, double-blind, placebo-controlled, clinical trial comprised outpatients from Guadalajara, Mexico. The inclusion criteria were either gender, age 35–80 years, type 2 diabetes, glycated hemoglobin ≤10%, diabetic polyneuropathy stage 1/2, and signed informed consent. Patients who were taking antioxidant therapy or statins, had hypersensitivity to drugs, experienced organ failure, were pregnant or breastfeeding, or had other types of neuropathy were excluded. We assigned patients to placebo, ezetimibe/simvastatin 10/20 mg, or rosuvastatin 20 mg, and the primary outcomes were 8-hydroxy-2′-deoxyguanosine (8-OHdG) for DNA damage, 8-oxoguanine-DNA- N -glycosilase (hOGG1) for DNA repair, and superoxide dismutase (SOD). Seventy-four patients were recruited. Nine patients were included as negative controls. There were no differences in 8-OHdG between the healthy subjects (4.68 [3.53–6.38] ng/mL) and the DPN patients (4.51 [1.22–9.84] ng/mL), whereas the hOGG1 level was 0.39 (0.37–0.42) ng/mL in the healthy subjects and 0.41 (0.38–0.54) ng/mL in patients with DPN at baseline ( p = 0.01). SOD decreased significantly in patients with DPN (5.35 [0.01–17.90] U/mL) compared with the healthy subjects (9.81 [8.66–12.61] U/mL) at baseline ( p < 0.001). No significant changes in DNA biomarkers were observed in any group between baseline and final levels. We noted a rise in hOGG1 in patients with DPN, without modifications after treatment. There was a slight, albeit insignificant, increase in SOD in patients who were on statins

Markers of Oxidative Stress and Inflammation in Ascites and Plasma in Patients with Platinum-Sensitive, Platinum-Resistant, and Platinum-Refractory Epithelial Ovarian Cancer

Diverse proinflammatory biomarkers and oxidative stress are strongly associated with advanced epithelial ovarian cancer (EOC). Objective. To determine the behavior of markers of oxidative stress and inflammation in plasma and ascites fluid in patients with platinum-sensitive, platinum-resistant, and platinum-refractory EOC. Methods. A prospective cohort study. The colorimetric method was used to determine levels of the markers 8-isoprostanes (8-IP), lipid peroxidation products (LPO), and total antioxidant capacity (TAC) in plasma and ascites fluid; and with ELISA, the levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were determined in patients with EOC. Results. In ascites fluid, a significant increase in 8-IP versus baseline plasma levels was found (p=0.002). There was an important leakage of the TAC levels in ascites fluid versus baseline plasma levels (p<0.001). The IL-6 was elevated in ascites fluid versus baseline plasma levels (p=0.003), and there were diminished levels of TNF-α in ascites fluid versus baseline plasma levels (p=0.001). Discussion. We hypothesize that the ascites fluid influences the behavior and dissemination of the tumor. Deregulation between oxidants, antioxidants, and the proinflammatory cytokines was found to vary among platinum-sensitive, platinum-resistant, and platinum-refractory patients