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TIP. Revista especializada en ciencias químico-biológicas
versão impressa ISSN 1405-888X
TIP vol.8 no.2 Ciudad de México Dez. 2005
Nota científica
Investigación y desarrollo de un fármaco para el tratamiento de la cirrosis
Research and development of a drug for the treatment of cirrhosis
1Depto. de Biología Celular, Instituto de Fisiología Celular, UNAM. C.P. 04510, México D.F.
La cirrosis es una de las causas más comunes de muerte en el mundo ya que la disfunción hepática conduce a una condición letal. Su etiología es diversa y no existe un tratamiento efectivo para prevenir o revertir esta patología, sin embargo, el riesgo de complicaciones como sepsis, peritonitis, sangrados e hipertensión y desarrollo de carcinoma hepático aumenta. En esta nota describimos brevemente las características estructurales y funcionales del tejido hepático normal comparándolas con los cambios que ocurren a lo largo del desarrollo de esta patología. comentamos el trabajo que hemos realizado en el laboratorio en un modelo experimental de hepatotoxicidad aguda y crónica usando al nucleósido adenosina como hepatoprotector. A través de sus efectos antifibrogénicos en el metabolismo de colágena estimula su degradación al disminuir los inhibidores y favorece la recuperación de la función hepática, principalmente su capacidad de regeneración. También comentamos aspectos importantes y necesarios que permitan la aplicación de estos hallazgos de investigación básica a un modelo experimental de pacientes con este padecimiento y enumeramos una serie de estudios de tipo farmacológico que permitirán la aplicación de este compuesto a pacientes.
Palabras Clave: Aplicación farmacéutica; cirrosis; colágena; hepatotoxicidad; inhibidores de metaloproteinasas
Cirrhosis is one of the most common causes of mortality worldwide because hepatic dysfunction constitutes a potentially lethal condition. Its etiology is variable and there's no treatment for prevention or regression of the pathology. But there is an increased risk of sepsis, bacterial peritonitis, variceal bleeding, portal hypertension and development of hepatocellular carcinoma. This document briefly describes the structure and functions of the normal liver in comparison to the cirrhotic liver. our experience regarding the studies of acute and chronic experimental hepatotoxicity using the nucleoside adenosine as an hepatoprotector is commented. The antifibrogenic effect of this compound increases collagen degradation through decreasing liver TIMPs levels, favoring normalization of liver function mainly by the promotion of hepatocyte proliferation. Comments on important aspects needed to promote the application of these findings in the experimental model to cirrhotic patients are presented as well. Some pharmacological and toxicological studies which lead us to the human use of this compound are also discussed.
Key Words: Pharmaceutical applications; cirrhosis; collagen; hepatotoxicity; tissue inhibitors metalloproteinases
Agradecimientos
En la etapa de investigación: Biól. Susana Vidrio, QFB Lucía Yáñez Maldonado, Juan Manuel Barbosa (Unidad de Cómputo), MC Rodolfo Paredes (Unidad de Microscopía), Dr. Alberto Aranda y Dra. María Lilia Loredo (Instituto Nacional de Cardiología).
En la etapa de desarrollo y aplicación: Dr. Adolfo García Sáinz (Director del Instituto de Fisiología Celular, UNAM), Lic. Gilberto Escamilla (Secretario Administrativo, Instituto de Fisiología Celular, UNAM), Dr. Francisco Hernández (Depto. de Farmacia, Facultad de Química), Ing. Antonio Galán, Ing. Georgina Valdespino (Coordinación de Vinculación UNAM), Dr. René Drucker Colín, Dra. Carmen Álvarez Buya, Quím. Marta Carrasco, Dr. Raúl Herrera, Dr. Edmundo de Alba, M. en C. Mario Gaytán, Lic. Patricia Morales (Coordinación de la Investigación Científica, UNAM), Lic. Carlos Bazdrech (CIDE), Ing. Jaime Uribe (Director General, Probiomed), Dr. Carlos Robles (Director de Planeación, Probiomed) e Ing. Jaime Parada (Director del CONACyT). Apoyo Clínico: Dr. Norberto García García y Dra. Laura Ladrón de Guevara.
Apoyo financiero: DGAPA ( IN206195, IN2123997, IN226199), CONACYT41433-Q, Corporativa de Fundaciones, A.C. Laboratorios Sophia.
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Recibido: 03 de Octubre de 2005; Aprobado: 29 de Noviembre de 2005
Este es un artículo publicado en acceso abierto bajo una licencia Creative Commons
