Evolución del concepto de “Estrés Oxidativo”: medio siglo de aportes de nuestra Facultad.

Rafael Radi

Resumen


La siguiente revisión presenta algunos elementos acerca de la evolución del concepto de “Estrés Oxidativo”, que van desde las primeras observaciones bioquímicas en sistemas enzimáticos hasta aproximaciones terapéuticas actuales a nivel preclínico. En el transcurso de ya más de medio siglo de aportes, se destaca en etapas tempranas del desarrollo del concepto la participación de investigadores que trabajaron activamente en la Facultad de Medicina, Universidad de la República (Montevideo, Uruguay) y en particular en su Departamento de Bioquímica, incluyendo al Profesor Visitante John Totter y al Profesor Eugenio Prodanov. El entendimiento de los procesos metabólicos que conducen a la formación y eliminación de especies oxidantes y radicales libres, y el desarrollo de técnicas para su identificación, detección y cuantificación ha sido un foco central del área. Se analiza el desarrollo y evolución del concepto de “Estrés Oxidativo” que se define actualmente como una situación de desbalance metabólico que conduce a alteración de la señalización redox y/o daño oxidativo facilitando el desarrollo y progresión de patología degenerativa e inflamatoria. Los fenómenos oxidativos también son utilizados por células del sistema inmune como mecanismo citotóxico contra patógenos invasores. Un avance importante del área se dio con el reconocimiento que el metabolismo del radical óxido nítrico se conecta con procesos oxidativos, en particular a través de su reacción difusional con el radical superóxido para rendir peroxinitrito, un peróxido y nucleófilo inestable y reactivo en sistemas biológicos. La mejor comprensión de los mecanismos intra y extracelulares de formación de especies oxidantes, incluyendo el rol de la disfunción mitocondrial, y los mecanismos de señalización redox, están dando lugar al desarrollo de estrategias nutricionales y farmacológicas con capacidad de modular in vivo fenómenos oxidativos asociados a patología. He seleccionado observaciones y trabajos con énfasis bioquímico que considero relevantes a nivel universal, relacionándolos e integrándolos con aportes que se han realizado desde nuestra Facultad en el área de estrés oxidativo.


Palabras clave


Oxidantes, radicales libres, quimioluminiscencia, antioxidantes, señalización redox, óxido nítrico, peroxinitrito, estrés oxidativo

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Referencias


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