Antioxidant Enzymes and Their Potential Use in Breast Cancer Treatment.

According to the World Health Organization (WHO), breast cancer (BC) is the deadliest and the most common type of cancer worldwide in women. Several factors associated with BC exert their effects by modulating the state of stress. They can induce genetic mutations or alterations in cell growth, encouraging neoplastic development and the production of reactive oxygen species (ROS). ROS are able to activate many signal transduction pathways, producing an inflammatory environment that leads to the suppression of programmed cell death and the promotion of tumor proliferation, angiogenesis, and metastasis; these effects promote the development and progression of malignant neoplasms. However, cells have both non-enzymatic and enzymatic antioxidant systems that protect them by neutralizing the harmful effects of ROS. In this sense, antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), thioredoxin reductase (TrxR), and peroxiredoxin (Prx) protect the body from diseases caused by oxidative damage. In this review, we will discuss mechanisms through which some enzymatic antioxidants inhibit or promote carcinogenesis, as well as the new therapeutic proposals developed to complement traditional treatments.

Cellular Compartmentalization, Glutathione Transport and Its Relevance in Some Pathologies.

Reduced glutathione (GSH) is the most abundant non-protein endogenous thiol. It is a ubiquitous molecule produced in most organs, but its synthesis is predominantly in the liver, the tissue in charge of storing and distributing it. GSH is involved in the detoxification of free radicals, peroxides and xenobiotics (drugs, pollutants, carcinogens, etc.), protects biological membranes from lipid peroxidation, and is an important regulator of cell homeostasis, since it participates in signaling redox, regulation of the synthesis and degradation of proteins (S-glutathionylation), signal transduction, various apoptotic processes, gene expression, cell proliferation, DNA and RNA synthesis, etc. GSH transport is a vital step in cellular homeostasis supported by the liver through providing extrahepatic organs (such as the kidney, lung, intestine, and brain, among others) with the said antioxidant. The wide range of functions within the cell in which glutathione is involved shows that glutathione's role in cellular homeostasis goes beyond being a simple antioxidant agent; therefore, the importance of this tripeptide needs to be reassessed from a broader metabolic perspective.

NOX as a Therapeutic Target in Liver Disease.

The nicotinamide adenine dinucleotide phosphate hydrogen oxidase (NADPH oxidase or NOX) plays a critical role in the inflammatory response and fibrosis in several organs such as the lungs, pancreas, kidney, liver, and heart. In the liver, NOXs contribute, through the generation of reactive oxygen species (ROS), to hepatic fibrosis by acting through multiple pathways, including hepatic stellate cell activation, proliferation, survival, and migration of hepatic stellate cells; hepatocyte apoptosis, enhancement of fibrogenic mediators, and mediation of an inflammatory cascade in both Kupffer cells and hepatic stellate cells. ROS are overwhelmingly produced during malignant transformation and hepatic carcinogenesis (HCC), creating an oxidative microenvironment that can cause different and various types of cellular stress, including DNA damage, ER stress, cell death of damaged hepatocytes, and oxidative stress. NOX1, NOX2, and NOX4, members of the NADPH oxidase family, have been linked to the production of ROS in the liver. This review will analyze some diseases related to an increase in oxidative stress and its relationship with the NOX family, as well as discuss some therapies proposed to slow down or control the disease's progression.

El aprendizaje basado en problemas como una estrategia didáctica para la educación médica / Problem-Based Learning as a Didactic Strategy for Medical Education

Resumen: La educación médica se enfrenta a nuevos retos para el desarrollo y adquisición de competencias en los estudiantes de medicina, y aunque existen diversas estrategias didácticas que pueden permitir enfrentar dichos retos, el aprendizaje basado en problemas (ABP) es una de las más eficaces para lograrlo; sin embargo, con el fin de aplicarlo de la mejor manera, es necesario entender el método y las diversas formas en que se ha implementado, así como identificar las dificultades y desventajas que se presentan. El presente artículo tiene como objetivo realizar una revisión sobre el método del ABP, sus ventajas y desventajas, así como algunos errores comunes al momento de implementarlo, haciendo hincapié en el contexto mexicano.

Abstract: Medical education faces new challenges in the development and acquisition of competencies in medical students, and although there are teaching strategies that can be helpful to reach this goal, PBL is one of the best strategies. In order to take advantage of PBL, it is important to understand the method and the various ways in which it has been implemented, as well as to identify the difficulties and disadvantages of PBL. The objective of this article is to review the PBL method, its advantages and disadvantages, and some frequent mistakes in its implementation, emphasizing the Mexican context.

El papel de las especies reactivas de oxígeno y de nitrógeno en algunas enfermedades neurodegenerativas / The role of reactive oxygen and nitrogen species in some neurodegenerative diseases

Resumen Las especies reactivas de oxígeno y nitrógeno son moléculas que se generan a partir del metabolismo celular fisiológico; sin embargo, cuando existe un desequilibrio entre la producción de radicales libres y los mecanismos antioxidantes se genera estrés oxidante. El estrés oxidante se ha asociado con el desarrollo y progresión de enfermedades neurodegenerativas como Alzheimer, Parkinson y Huntington. Dado que el inicio del estrés oxidante es imperceptible y aún no se cuenta con estudios de laboratorio que determinen el impacto de los radicales libres en pacientes con enfermedades neurodegenerativas, es importante dilucidar el papel de estos en los procesos neurodegenerativos con el fin de tener indicios sólidos sobre las posibles dianas de tratamiento y prevenir el daño progresivo en este tipo de enfermedades.

Abstract The reactive oxygen and nitrogen species are molecules that are generated from the physiological cellular metabolism. However, when there is an imbalance between the production of free radicals and the antioxidant mechanisms, oxidative stress is generated. Oxidative stress has been associated with the development and progression of neurodegenerative diseases such as Alzheimer, Parkinson and Huntington, given that the onset of oxidative stress is imperceptible and that there are still no laboratory studies that can determine the impact of free radicals in patients with neurodegenerative diseases. It is important to elucidate the role of free radicals in neurodegenerative processes in order to have solid indications about the possible treatment targets and to prevent the progressive damage in this type of diseases.

ß- Adrenoceptors activate hepatic glutathione efflux through an unreported pathway.

The physiological regulation of hepatic glutathione efflux by catecholamines is poorly understood. The purpose of this work was to review the role of adrenergic receptors (AR) on total glutathione (GT) efflux in rat liver. Two models were used: isolated hepatocytes and perfused livers. In hepatocytes 10 µM adrenaline (Adr), but not isoproterenol (Iso) a ß-AR agonist, or phenylephrine (Phe) an α1-AR agonist, (in a Krebs-Henseleit buffer (KHB) enriched with Ca2+ and some aminoacids) increased in 13% GT efflux. In livers perfused with KHB, Adr or Iso at 1 µmolar doses (but not Phe) stimulated 11-fold initial velocity of GT release, but only during the first 2 min of perfusion. This immediate response progressively disappeared during the following 15 min of perfusion. A second phase of GT efflux, observed between 2 and 14 min of perfusion, mimics the one reported earlier in isolated hepatocytes. The ED50 for Adr and Iso activation are in the range of 320 nM and 10 nM, respectively. Iso-mediated GT release requires Ca2+ to work, and was prevented by H89, glibenclamide, cystic fibrosis transmembrane regulator (CFTR) antibodies, and a direct CFTR inhibitor. This short-lived GT release system is associated to PKA activation and probably operates through CFTR.