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Friday, July 5, 2013

Sulforaphane Accelerates Acetaldehyde Metabolism by Inducing Aldehyde Dehydrogenases: Relevance to Ethanol Intolerance



Many East Asians are highly intolerant to even modest alcohol consumption. These individuals accumulate acetaldehyde, the primary metabolite of ethanol, because of a genetic polymorphism of aldehyde dehydrogenase (ALDH) that metabolizes acetaldehyde to nontoxic acetate. The aim of these studies is to upregulate ALDH by dietary means, thereby reducing acetaldehyde toxicity.                    

Sulforaphane [SF, 1-isothiocyano-4-(methylsulfinyl)butane] derived from its glucosinolate precursor contained in cruciferous vegetables and related inducers of the Keap1/Nrf2/ARE pathway were assessed for their potencies to induce ALDH in murine hepatoma Hepa1c1c7 cells. Inducer potencies for ALDH were compared with those for NQO1, a prototypical cytoprotective enzyme present downstream of the Keap1/Nrf2/ARE pathway. SF (5 or 20 ┬Ámol/day) was fed to CD-1 mice for 7 days prior to a single administration of ethanol, and then ALDH induction in organs and pharmacokinetics of acetaldehyde was examined.

In addition to SF, other electrophiles, including many Michael reaction acceptors, induce ALDH. Potencies of these agents as inducers parallel their activities in inducing NQO1, and are also dependent on Nrf2. In mice, in vivo, feeding of SF induced tissue ALDH and dramatically increased (doubled) the rate of elimination of acetaldehyde arising from the administration of ethanol.

SF and other edible phytochemicals may ameliorate the alcohol intolerance of individuals who are polymorphic with respect to ALDH.    



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