ABSTRACT
La diabetes mellitus sobreviene cuando el páncreas produce una cantidad insuficiente de insulina o el cuerpo no utiliza de manera correcta esta hormona. Generalmente debido a su patogenia se clasifica en dos tipos: diabetes mellitus tipo 1 (insulino dependiente) y diabetes mellitus tipo 2. En los últimos años se ha convertido a nivel mundial en una de las principales causas de muerte y factor de riesgo para el desarrollo de diversas patologías. Debido a la implicancia en la salud humana y su cada vez mayor distribución a nivel mundial se ha convertido en uno de los tópicos de investigaciones de diversos grupos, quienes buscan comprender mejor su patogenia y desarrollar posibles tratamientos tanto a nivel molecular como celular. Las actuales técnicas de investigación desarrolladas abarcan modelos animales a los cuales se les induce esta patología químicamente, cepas de ratones que la desarrollan espontáneamente luego de cruces selectivos, y los creados por las más nuevas técnicas de ingeniería genética. A pesar de todo el esfuerzo no existe un único modelo que nos presente todo el abanico de posibilidades que se presentan en los seres humanos. Es por ello que se presentan diversos modelos con diferentes características, cada uno nos ayudará a comprender un poco más esta enfermedad.
Diabetes mellitus occurs when the pancreas produces an insufficient amount of insulin or the body does not use this hormone correctly. Generally, due to the pathogenesis, it is classified into two types: type 1 diabetes mellitus (insulin dependent) and type 2 diabetes mellitus. In recent years, it has become one of the main causes of death worldwide and a risk factor for the development of various pathologies. Due to the implication in human health and its increasing distribution worldwide, it has become one of the research topics of several groups, who are seeking to better understand diabetes pathogenesis and develop possible treatments both at the molecular and cellular level. The current research techniques developed include animal models in which this pathology is chemically induced, strains of mice that develop it spontaneously after selective crossing, and those created by the newest genetic engineering techniques. Despite all the effort, there is no single model that presents us with the full range of possibilities that occur in human beings. That is why various models with different characteristics are presented, each one will help us understand this disease a little more
Subject(s)
PathologyABSTRACT
El hígado es el órgano principal del cuerpo encargado de mantener la homeostasis interna, además cumple un rol fundamental en el metabolismo de medicamentos (xenobióticos) por lo tanto es vulnerable a lesiones fisiológicas o anatómicas. La lesión hepática inducida por fármacos (DILI) es la causa más común del fracaso del desarrollo pre-clínico y clínico de nuevos medicamentos, y de las advertencias de recuadro negro y el retiro de un medicamento del mercado. Por lo tanto, representa un problema grave para las industrias farmacéuticas, así también para el paciente, profesionales de la salud y las entidades reguladoras. Cabe mencionar que existen dos tipos de lesión hepática inducida por fármacos: farmacológicas o intrínsecas y la idiosincrásica. Durante la etapa pre-clínica del proceso de desarrollo de un medicamento se realiza un panel de cribado a los medicamentos candidatos empleando modelos celulares in vitro que incluyen sistemas de cultivos en 2D, 3D y líneas celulares de hepatoma humano, aunque también existen otros enfoques en el cual utilizan al pez cebra (reemplazo a los modelos animales) o modelos celulares basados en cribado de alto contenido. Posteriormente se emplean animales que, aunque presenten diferencias específicas respecto al humano a nivel hepatocelular igualmente se utiliza, para realizar predicciones cuantitativas y cualitativas de las principales propiedades farmacodinámicas, farmacocinéticas y toxicológicas del medicamento candidato. Actualmente existe un mayor esfuerzo para ir mejorando algunos modelos in vitro ya existentes, acoplando alguna herramienta o modificándolo genéticamente hacia el producto de interés proporcionando nuevos enfoques útiles para la predicción potencial tóxico a nivel hepático de los medicamentos candidatos.(AU)
The liver is the main organ of the body whose function is to maintain internal homeostasis, it also plays a fundamental role in the metabolism of drugs (xenobiotics), therefore it is vulnerable to physiological or anatomical injuries. Drug-induced liver injury (DILI) is the most common cause of preclinical and clinical development failure of new drugs, black box warnings, and drug recall. Therefore, it represents a serious problem for the pharmaceutical industries, as well as for the patient, health professionals and regulatory entities. It should be mentioned that there are two types of drug-induced liver injury: pharmacological or intrinsic and idiosyncratic. During the pre-clinical stage of the drug development process, candidate drugs are screened using in vitro cell models that include 2D, 3D culture systems and human hepatoma cell lines, although other approaches use zebrafish (replacement for animal models), or cell models based on high content screening. Subsequently, animals are used, which despite having specific differences with respect to humans at the hepatocellular level are also used to make quantitative and qualitative predictions of the main pharmacodynamic, pharmacokinetic and toxicological properties of the candidate drug. Currently, there is a major effort to improve some existing in vitro models, coupling a tool or genetically modifying it towards the product of interest, providing new useful approaches for the potential prediction of liver toxicity, of the candidate drugs.(AU)
Subject(s)
In Vitro Techniques , Liver , Zebrafish , Drug IndustryABSTRACT
Liver and kidney are vital organs for body homeostasis and are exposed to damage or injury of various origins. Many medicinal plants have proved to be effective for hepatic and renal diseases. This study aimed to test the effect of Prosopis ruscifolia Griseb. leaves extract on acetaminophen-induced hepatotoxicity and gentamicin-induced nephrotoxicity. The experiment was carried out in mice, 300 mg/kg of acetaminophen, i.p., and 135 mg/kg of gentamicin were used to induce liver and kidney damage, respectively. Silymarin was used as protective control drug. For estimating the liver function, alkaline phosphatase (ALP), aspartate aminotransferase (AST or GOT), and alanine aminotransferase (ALT or GPT) were measured; and creatinine, urea, and uric acid were determined in order to verify kidney functionality. The results showed that the extract has both hepatoprotective and nephroprotective effect. This is evidenced by reduced values of the level of GOT, GPT, and ALP, in mice co-administered, p.o., with P. ruscifolia; and by the reduction of serum creatinine in mice with gentamicin induced kidney damage. These values showed statistically significant difference when compared with those of pathological group. The alcoholic extract of P. ruscifolia denoted hepatoprotective and nephroprotective effects.