Ethanol induces heterogeneous reduction of cytochrome aa3 within perfused rat liver lobule assessed using...

The redox state of cytochrome aa3 was measured at microspots (20 microns diameter) within the lobule of perfused rat livers, using reflectance microspectroscopy, and the effect of ethanol infusion on sublobular distribution of the redox states was evaluated. A sigmoidal relationship was observed between oxygen delivery and the reduction of cytochrome aa3 in both the periportal and pericentral regions of the liver lobule when the influent O2 concentration was decreased in a graduated manner. This sigmoidal curve was shifted to the more reduced state by ethanol infusion, with ethanol (25-100 mM) increasing the degree of cytochrome aa3 reduction in a dose-dependent manner according to the distance from the periportal region along a sinusoid. This increase was spatially heterogeneous within a liver lobule. These data indicate that ethanol accelerates cytochrome aa3 reduction, with a distinct gradient of reduction along sinusoids but a heterogeneous distribution within the liver lobule.