Copyright ©2009 The WJG Press and Baishideng.
World J Gastroenterol. Oct 21, 2009; 15(39): 4865-4876
Published online Oct 21, 2009. doi: 10.3748/wjg.15.4865
Table 1 Mechanisms that favor high sensitivity of fatty liver to drug toxicity and necrotic cell death
Initial changeIntermediate effectsConsequences
Increased bioactivation (microsomal CYP 450s)Higher amount of toxic metabolitesConsumption of antioxidants
Increased release of ROSLipid peroxidation
Mitochondrial dysfunctionDecreased energy production (ATP) and cytochrome c contentOver-expression of uncoupling protein 2
Increased Ca2+ efflux
Increased release of ROS and NO derivativesProtein oxidation and nitration
Pores opening and increased membrane permeabilityExpression of FAS ligands
Calpain activation and protein cleavage
Impaired intracellular signaling and traffickingAlterations of nuclear receptors and sensorsDefective transcription of repair mechanisms
Increased DNA fragmentation rate
Activation of non-parenchymal cells (Kupffer cells) and enzymesIncreased release of transforming growth factor-β1, p53, TNF-αInflammation and pro-oxidant attack
Increased NADPH oxidase activity