The effect of intracellular redox state on chloral hydrate metabolism in the perfused rat liver

肝細胞内酸化還元レベルの抱水クローラル代謝に及ぼす影響

The effect of intracellular redox state on chloral hydrate metabolism in the perfused rat liver

Creators Aoki Tatsuya

Chloral hydrate (CH), an intermediate metabolite of trichloroetylene, is reduced to trichloroethanol (TCE) by alcohol dehydrogenase and aldehyde reductase and is also oxidized to trichloroacetic acid (TCA) bu the noicotinamide adenine dinucleotide (NAD)-deoendent enzyme, CH dehydrogenase. Alcohol dehydrogenase requires reduced NAD (NADH), aldehyde reductase requires reduces nocotinamide adenine dinucletide phosphate (NADPH) and CH dehydrogenase reguires NAD to complete the reactions. It has been unclear which reaction is predominant at the pathological redox level in intact liver cells or at the pathological level. It is very important to study this question because of the estimation of biological exposure indices. We perfused the livers of well-fed rats with Krebs-Ringer buffer solution containinf 0.1mM pyruvate/1.0mM lactate. The levels of TCE and TCA in the effuent were measured by gas chromatography. When a low concentration (below 0.25mM) of CH was administrated, more TCA than TCE was produced. When a high concentration of CH was administrated (over 0.5mM), TCE production was greater. When 10mM lactate was added to the perfusate in order to reduce the pyridine nucleotides in the liver cells. The TCE/TCA ratio increased. On the other hand, the TCE/TCA ratio tended to fall follwing the addition of 5.0mM pyruvate. The metabolism of choral hydrate under anoxic sonditions was investigated in the non-circulating, hemoglobin-free liver perfusion system. CH uptake in the anoxic liver decreased to about 80% of that in the ixygen-rich liver. The reduction of CH to TCE increased and the oxidation of CH to TCA decreased. The TCE/TCA ratio increased

[ISSN]0513-1731

[NCID]AN00243156