Dependence of ethanol-induced redox shift on hepatic oxygen tensions prevailing in vivo.
Since many metabolic derangements induced by ethanol have been linked to the redox shift, we studied the effects of oxygen in the range of tensions prevailing in vivo along the sinusoids on both the basal redox state and the shift induced by ethanol. The redox state of nicotinamide nucleotides was assessed by surface NADH fluorescence and that of cytochrome oxidase by transmittance dual-wavelength spectrophotometry in the hemoglobin-free, perfused rat liver. In the absence of ethanol, varying the oxygen tensions within the physiological range produced a redox gradient of both cytochrome oxidase and NAD+, with a more reduced state at tensions normally prevailing in perivenular zones. The degree of reduction of cytochrome oxidase at these physiological oxygen tensions was associated with no impairment in the ability of the liver to consume oxygen and to produce ATP, suggesting lack of cellular anoxia. 25 mM ethanol increased hepatic oxygen consumption, but had no direct effect on the state of reduction of cytochrome oxidase. The effects of ethanol and oxygen tensions on NADH fluorescence were additive, indicating that a greater redox shift should occur when ethanol is oxidized at oxygen tensions similar to those normally prevailing in prievenular zones than at those in periportal zones. This dependence of the ethanol-induced redox shift on oxygen tensions may contribute to the selective perivenular hepatotoxicity of alcohol.
Jauhonen
V P
VP
Baraona
E
E
Lieber
C S
CS
Hassinen
I E
IE
D000818:Animals; D003576:Electron Transport Complex IV / Q000032:analysis; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000032:analysis; D010084:Oxidation-Reduction; D010100:Oxygen / Q000032:analysis*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D009243:NAD; D000431:Ethanol; D003576:Electron Transport Complex IV; D010100:Oxygen