Biochemical mechanisms in drug-induced liver injury: Certainties and doubts

Figure 3 Schematic representation of mitochondrial oxido-reductase system. Several drug molecules directly or after metabolic release of toxic intermediates can cause mitochondrial alterations at different levels. The following impairment of the energetic and redox balance finally triggers apoptotic or necrotic processes according to a poor or sufficient ATP level. Important regulatory mechanisms rely on the glutathione dependent redox status of proteins. GSH: Reduced glutathione; GSSG: Oxidized glutathione; GSH-Px: Glutathione peroxidase; GSSG-RX: Glutathione reductase; iNOS: Inducible nitric oxide synthetase; NO: Nitric oxide; PSH: Protein sulphydrils; PS-SG: Protein mixed disulfides; PS-SP: Protein-protein disulfides; TRx: Thioredoxin; TRx-R: Thioredoxin reductase; TR-S₂: Oxidized thioredoxin.