Epalrestat suppresses inflammatory response in lipopolysaccharide-stimulated RAW264.7 cells

Introduction and objectives: Lipopolysaccharide (LPS) is a potent inducer of inflammatory response. Inflammation is a major risk factor for many diseases. Regulation of inflammatory mediator and pro-inflammatory cytokine levels could be a potential therapeutic approach to treat inflammatory injury. The purpose of the present study was to determine whether epalrestat (EPS), which is used for the treatment of diabetic neuropathy, suppresses inflammatory response in LPS-stimulated RAW264.7 cells. Material and methods: The effects of EPS at near-plasma concentration on the levels of pro-inflammatory cytokines and inflammatory mediators was examined using by MTS assay, quantitative RT-PCR analysis, and western blotting in LPS-stimulated RAW264.7 cells. Results: EPS suppressed mRNA and protein expression levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNFα, in RAW264.7 cells stimulated with LPS. EPS also affected inflammatory mediators such as iNOS and NF-κB in LPS-stimulated RAW264.7 cells. Conclusions: In this study, we demonstrated for the first time that EPS suppresses inflammatory response in LPS-stimulated RAW264.7 cells. From these results, we propose that targeting the regulation of pro-inflammatory cytokine levels and inflammatory mediators by EPS is a promising therapeutic approach to treat inflammatory injury. It is expected that EPS, whose safety and pharmacokinetics have been confirmed clinically, would be useful for the treatment of inflammatory diseases (AU)

Síndrome metabólico y diabetes mellitus / Metabolic syndrome and diabetes mellitus

La diabetes mellitus (DM) es una enfermedad metabólica crónica que está adquiriendo en los últimos años proporciones de auténtica epidemia. Se asocia frecuentemente con obesidad, alteraciones del metabolismo lipídico y proteínico, así como con hipertensión arterial y otros factores de riesgo cardiovascular, lo que constituye el síndrome metabólico. La DM tipo 2 (DM2) es un factor de riesgo importante para la enfermedad coronaria y la aterosclerosis precoz. Su etiopatogenia es multifactorial y está muy relacionada con la resistencia insulínica (RI), que es el proceso fisiopatológico común al conjunto de factores de riesgo cardiovascular. Respecto a la prevención y el tratamiento de la DM2, es fundamental la modificación del estilo de vida, con especial hincapié en la alimentación equilibrada y la introducción del ejercicio físico aeróbico en la vida cotidiana. Cuando las pautas higiénico-dietéticas no son suficientes, se debe recurrir a fármacos que actúen sobre la diana de la resistencia insulínica, como la metformina y las tiazolidinas (AU)

Diabetes mellitus is a chronic metabolic disease that has acquired the nature of an epidemic in recent years. It is frequently associated with obesity, abnormalities of the lipid and protein metabolism, high blood pressure, and other cardiovascular risk factors, which are often clustered together in the metabolic syndrome. Type 2 diabetes mellitus is an important risk factor for coronary disease and premature atherosclerosis. It has a multifactorial pathogenesis and it is closely linked to insulin resistance, which is also involved in the pathophysiology of cardiovascular risk factors associated with metabolic syndrome. One fundamental intervention for the prevention and treatment of type 2 diabetes mellitus is lifestyle modification, in particular the adoption of a balanced diet and the inclusion of aerobic physical activity in daily life. When these measures are insufficient, the use of drugs that target insulin resistance, such as metformin and thiazolidinediones, is necessary (AU)