Interference of ethanol with the metabolism of gamma‐hydroxybutyrate (GHB) in the perfused rat liver

GHB is both a brain metabolite and a drug of abuse (date rape drug). There are contradictory reports on the effect of ethanol on the metabolism of GHB in vivo. Since the liver appears to be the main site of GHB metabolism in vivo, we measured the uptake of GHB by perfused rat livers. Livers from overnight‐fasted rats were perfused with non‐recirculating BSA‐free buffer with 4 mM glucose, or recirculating buffer containing 4% BSA and 4 mM glucose. The uptake of GHB was 130 to 180 nmol/g × min, and was not accelerated by glucuronate, as was hypothesized from previous in vivo studies. Adding lactate + pyruvate (5 mM total concentration) with [lactate]/[pyruvate] ratios ranging from 0.1 to 100 did not affect GHB uptake. Ethanol inhibited GHB uptake by half, but addition of pyruvate (0.2, 1.0, and 5 mM) restored GHB uptake to control levels. Thus, the effect of ethanol on GHB metabolism by the liver is influenced by the redox status of the NADH/NAD + system in the liver. Supported by NIH grant ES013925.