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Título : N-acetylcysteine, coenzyme Q10 and superoxide dismutase mimetic prevent mitochondrial cell dysfunction and cell death induced by d-galactosamine in primary culture of human hepatocytes
Autor : González, Raúl, Ferrín, Gustavo, Hidalgo, Ana B., Ranchal, Isidora, López-Cillero, Pedro, Santos-González, Mónica, López-Lluch, Guillermo, Briceño, Javier, Gómez, Miguel. A., Poyato, Antonio, Villalba, José M., Navas, Plácido, Mata, Manuel de la, Muntané, Jordi
Palabras clave : Antioxidants
Coenzyme Q
Fecha de publicación : 11-Jun-2009
Editor: Elsevier
Resumen: D-Galactosamine (D-GalN) induces reactive oxygen species (ROS) generation and cell death in cultured hepatocytes. The aim of the study was to evaluate the cytoprotective properties of N-acetylcysteine (NAC), coenzyme Q(10) (Q(10)) and the superoxide dismutase (SOD) mimetic against the mitochondrial dysfunction and cell death in D-GalN-treated hepatocytes. Hepatocytes were isolated from liver resections. NAC (0.5 mM), Q(10) (30 microM) or MnTBAP (Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (1mg/mL) were co-administered with D-GalN (40 mM) in hepatocytes. Cell death, oxidative stress, mitochondrial transmembrane potential (MTP), ATP, mitochondrial oxidized/reduced glutathione (GSH) and Q(10) ratios, electronic transport chain (ETC) activity, and nuclear- and mitochondria-encoded expression of complex I subunits were determined in hepatocytes. d-GalN induced a transient increase of mitochondrial hyperpolarization and oxidative stress, followed by an increase of oxidized/reduced GSH and Q(10) ratios, mitochondrial dysfunction and cell death in hepatocytes. The cytoprotective properties of NAC supplementation were related to a reduction of ROS generation and oxidized/reduced GSH and Q(10) ratios, and a recovery of mitochondrial complexes I+III and II+III activities and cellular ATP content. The co-administration of Q(10) or MnTBAP recovered oxidized/reduced GSH ratio, and reduced ROS generation, ETC dysfunction and cell death induced by D-GalN. The cytoprotective properties of studied antioxidants were related to an increase of the protein expression of nuclear- and mitochondrial-encoded subunits of complex I. In conclusion, the co-administration of NAC, Q(10) and MnTBAP enhanced the expression of complex I subunits, and reduced ROS production, oxidized/reduced GSH ratio, mitochondrial dysfunction and cell death induced by D-GalN in cultured hepatocytes.
Descripción : 12 páginas, 7 figuras, 1 tabla.
Versión del editor:
ISSN: 0009-2797
DOI: 10.1016/j.cbi.2009.06.003
Citación : Chemico-Biological Interactions 181(1): 95-106 (2009)
Referencias: PMID: 19523936
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