DAIDZIN SUPPRESSES ETHANOL-CONSUMPTION BY SYRIAN GOLDEN-HAMSTERS WITHOUT BLOCKING ACETALDEHYDE METABOLISM

Daidzin is a potent, selective, and reversible inhibitor of human mito chondrial aldehyde dehydrogenase (ALDH) that suppresses free-choice et hanol intake by Syrian golden hamsters. Other ALDH inhibitors, such as disulfiram (Antabuse) and calcium citrate carbimide (Temposil), have also been shown to suppress ethanol intake of laboratory animals and a re thought to act by inhibiting the metabolism of acetaldehyde produce d from ingested ethanol, To determine whether or not daidzin inhibits acetaldehyde metabolism in vivo, plasma acetaldehyde in daidzin-treate d hamsters was measured after the administration of a test dose of eth anol, Daidzin treatment (150 mg/kg per day i.p. for 6 days) significan tly suppresses (> 70%) hamster ethanol intake but does not affect over all acetaldehyde metabolism. In contrast, after administration of the same ethanol dose, plasma acetaldehyde concentration in disulfiram-tre ated hamsters reaches 0.9 mM, 70 times higher than that of the control . In vitro, daidzin suppresses hamster liver mitochondria-catalyzed ac etaldehyde oxidation very potently with an IC50 value of 0.4 mu M, whi ch is substantially lower than the daidzin concentration (70 mu M) fou nd in the liver mitochondria of daidzin-treated hamsters. These result s indicate that (i) the action of daidzin differs from that proposed f or the classic, broad-acting ALDH inhibitors (e.g., disulfiram), and ( ii) the daidzin-sensitive mitochondrial ALDH is not the one and only e nzyme that is essential for acetaldehyde metabolism in golden hamsters .