IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Hippocampal apoptosis in a low-grade hepatic encephalopathy model.
Autor/es:
PERAZZO, J.C.; LORES-ARNAIZ, S.; ROSELLÓ, D.M.; CZERNICZYNIEC, A.; LAGO, N.; TALLIS, S.; LEMBERG, A.; BUSTAMANTE, J.
Lugar:
Abano Terme (Padova), Italia
Reunión:
Simposio; 13th International Symposium on Hepatic Encephalopathy and Nitrogen Metabolism.; 2008
Institución organizadora:
International Society on Hepatic Encephalopathies and Nitrogen Metabolism
Resumen:
HIPPOCAMPAL APOPTOSIS IN A LOW-GRADE HEPATIC ENCEPHALOPATHY MODEL. Perazzo JC*.,S Lorez Arnaiz**, DM Roselló*, A Czerniczyniec**, N Lago*, S Tallis*, A Lemberg* & J Bustamante**. Laboratory of Free Radical Biology**, Laboratory of Portal Hypertension*, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956, C1113AAAD. Argentina        In previous reports we described mitochondrial hippocampal (H) morpho-functional alterations in blood brain barrier in rats with portal vein ligature (PVL). PVL induced portal hypertension, moderate hyperammonemia and is a valid model to study low-grade hepatic encephalopathy (lgHE). The aim of this work was to study early alterations in H in PVL rats.      Male Wistar rats weighing 250 g were divided into two groups: Group I, (n=12) with PVL and Group II, (n=12) was sham-operated. Ten days after PVL, portal pressure was recorded and plasma ammonia was determined. After that, hippocampal brains from both groups were dissected. To determine de presence of apoptosis the DNA decreases fragmentation method, TUNEL, was used. Isolation of mitochondrial fraction further mitochondrial purification for Western blot analysis was performed. Sub-mitochondrial membranes were obtained from mitochondria by twice freezing, thawing and homogenizing the suspension. Western blotting and chemiluminescence from H for Bax mitochondrial association was determined in mitochondrial purified fractions and mtNOS. Mitochondrial membrane potential in the hippocampus (cytometric, probe DIOC6) and release of  cytochrome c was registered. Results: TUNEL determination was positive in CA4 and CA1 H areas, Bax expression and release of cytochrome c was significantly higher in HP group and mtNOS expression and activity were significantly lower in HP. Extensive decrease in mitochondrial membrane potential was seen. Quantification of this process showed 30% depolarization in Group I when compared with Group II.      Conclusions: Early changes in H area in low-grade hepatic encephalopathy could be due to apoptosis triggered by the intrinsic mitochondrial pathway.