ABSTRACT
BACKGROUND: The physiopathology of the brain ischemia includes many events such as important apoptotic mechanisms were Fas protein is expressed. Statins have neuroprotector effects that are independent of their blood lipid reducing actions. OBJECTIVE: Study of the atorvastatin effect on Fas expression in brain ischemia. MATERIAL AND METHODS: Fifteen male Sprague Dawley rats were distributed in three groups (n=5), the control group without cerebral ischemia, in the other two experimental groups (1 and 2) a global cerebral ischemia were induced by respiratory arrest (D-tubocurarin). Experimental group 2 was treated with atorvastatin (10 mg/Kg/d, p.o.) during two weeks before the induction of the ischemia. Immunohistochemical study of brain frontal specimens was done by the Avidin-Biotin-Peroxidase method. RESULTS: Fas was expressed in 38% of cells in non ischemic brain, this expression increased to 63% of cells in ischemic brain samples (P = 0.0003) Fas expression in ischemia was significantly inhibited by atorvastatin in 23% (P = 0.0007). CONCLUSIONS: Atorvastatin decreased Fas expression in ischemic brain. This fact must be taken into account to explain the atorvastatin neuroprotection and suggests the potential use such as primary prevention for ischemic attacks.
Subject(s)
Apoptosis/drug effects , Brain Ischemia/metabolism , Heptanoic Acids/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Neuroprotective Agents/pharmacology , Pyrroles/pharmacology , fas Receptor/metabolism , Animals , Atorvastatin , Brain Ischemia/pathology , Male , Rats , Rats, Sprague-DawleyABSTRACT
Introducción: La fisiopatología de la isquemia cerebral involucramúltiples eventos, entre ellos, importantes mecanismos apoptóticos dondela proteína Fas es expresada. Las estatinas poseen efectos neuroprotectoresindependientes de sus acciones hipolipemiantes.Objetivo: Estudiar el efecto de la atorvastatina sobre la expresión deFas en tejido cerebral isquémico.Material y métodos: Quince ratas Sprague Dawley, machos, fuerondistribuidas en tres grupos (n = 5): un grupo control sin isquemia cerebral ydos experimentales (1 y 2) sometidos a isquemia cerebral global inducidapor paro respiratorio con D-tubocurarina. El grupo experimental 2 recibióatorvastatina durante las dos semanas previas a la inducción de isquemia(10 mg/kg/día, v.o.). Se realizó inmunohistoquímica por el sistema Avidina-Biotina-Peroxidasa a muestras de la corteza cerebral frontal.Resultados: Fas se expresó en el 38% de las células del tejido noisquémico. Esta expresión aumentó en el tejido cerebral isquémico a63% (P = 0,0003). La atorvastatina inhibió significativamente la expresiónde Fas en tejido cerebral isquémico en un 23% (P = 0,0007).Conclusiones: La atorvastatina disminuyó la expresión de Fas enisquemia cerebral, contribuyendo posiblemente a una inhibición de laapoptosis. Este mecanismo de acción pudiera explicar parte de su efectoneuroprotector. Estos hallazgos sugieren que la atorvastatina pudieraresultar beneficiosa en la prevención primaria de los ataques isquémicos
Background: The physiopathology of the brain ischemia includes many events such as important apoptotic mechanisms were Fas protein is expressed. Statins have neuroprotector effects that are independent of their blood lipid reducing actions. Objective: Study of the atorvastatin effect on Fas expression in brain ischemia. Material and methods: Fifteen male Sprague Dawley rats were distributed in three groups (n=5), the control group without cerebral ischemia, in the other two experimental groups (1 and 2) a global cerebral ischemia were induced by respiratory arrest (D-tubocurarin). Experimental group 2 was treated with atorvastatin (10 mg/Kg/d, p.o.) during two weeks before the induction of the ischemia. Inmunohistochemical study of brain frontal specimens was done by the Avidin- Biotin-Peroxidase method. Results: Fas was expressed in 38% of cells in non ischemic brain, this expression increased to 63% of cells in inchemic brain samples (P = 0.0003) Fas expression in ischemia was significantly inhibited by atorvastatin in 23% (P = 0.0007) Conclusions: Atorvastatin decreased Fas expression in ischemic brain. This fact must be taken into account to explain the atorvastatin neuroprotection and suggests the potential use such as primary prevention for ischemic attacks
