Figure 1.

Proposed oxaliplatin liver injury mechanisms of sinusoidal damage: first, oxaliplatin increases porosity of the sinusoidal endothelium cellular fenestrations, stimulating the release of free radicals and depletion of glutathione transferase, followed by an increase of metalloproteinases (MMP-2 and MMP-9). This damage favors the migration of erythrocytes into the space of Dissé and formation of perisinusoidal fibrosis. In this hypoxic situation, an increase of angiogenic factors (and activation of metalloproteinases in turn increasing vascular damage is induced. Second, nodular regenerative hyperplasia is favored by the chronic hypoxia of the centrilobular areas. Third, oxaliplatin can generate an obliteration of the blood capillaries and areas of parenchymal extinction that interrupt portal circulation and eventually elevate portal pressures.