Changes in liver nucleotide concentrations in experimental liver injury. 2. Acute ethanol poisoning

Abstract

Changes in the concentrations of nlcotinamide adenine dinucleotide (NAD,) reduced nicotinamide adenine dinucleotide (NADH2)nicotinamide adenine dinucleotide phosphate (NADP) and reduced nicotinamide adenine dinucleotide phosphate (NADPH2) in rat liver after a single intraperiton-eal injection of ethanol were determined at frequent stages during the ensuing poisoning. The concentrations of NAD and NADH2 in the liver show very rapid changes, such that the NAD:NADH2 ratio decreases from a control value of 4-110-47 to 2-16[plus or minus]D-14 within 3 minutes of the administration of ethanol. The ratio is still very low 5 hours later but has returned to normal approximately 13 hours after the injection of ethanol. Dosing rats with a much higher amount of ethanol (6-0 g. /kg. body weight instead of 2-4 g. Ag body weight) prolonged the effect; the NAD:NADH2 ratio was still decreased 13 hours after dosing, but was in the normal range 5 hours later. In contrast, no significant changes were found in the liver''s content of NADP and NADPH2 during the entire period of poisoning studied, other than a slight fall in the NADP concentration 60-90 minutes after dosing with ethanol. The relationship of the changes in NAD and NADH2 concentrations to the developing fatty liver are discussed, as are the implications of the lack of change in the NADP and NADPH2 contents. It is concluded that the changes in the NAD:NADHn ratio bear no apparent or direct relationship to the increased lipid content that occurs in the liver after treatment with ethanol.