Mice liver metabolism and defence mechanisms under oxidative stress-related conditions:Hypotaurine as selective hepatic antioxidant?

C. Zwingmann, C. Éthier, D. Leibfritz, M. Bilodeau Centre de Recherche, Laboratoire d'hepatologie cellulaire, Hospital Saint-Luc (CHUM), Montreal, Quebec, Canada, Department of Organic Chemistry, University of Bremen, Bremen, Germany Introduction Mitochondrial damage is being recognized as a key step in liver injury associated with oxidative stress. Mitochondria also have necessary roles in the genesis of apoptosis in certain cell types [1]. As mitochondrial function is tightly coupled to both production of free radicals and cellular energy production, changes in mitochondrial energy metabolism may be a central feature in liver injuries. Interestingly, a link between glucose metabolism and apoptosis has been reported recently [2]. The most widely used antidote to prevent oxidative damage to the liver is N-acetyl-cysteine (NAC), which is believed to exert its beneficial effect by the replenishment of the antioxidant glutathione (GSH). To clarify the involvement of hepatic intermediary metabolism in liver injury, we used ex vivo multinuclear NMR spectroscopy combined with in vivo injection of different C-labelled substrates 1) to characterize key metabolic pathways in mice liver at rest, 2) to investigate whether metabolic changes are associated with a) peroxide-mediated oxidative stress, b) oxidative stress due to mitochondrial impairment or c) anti-FAS mediated apoptosis, and 3) to adress whether NAC is involved in yet undescribed metabolic pathways of the liver under normal and oxidative-stress related conditions.