Acetaldehyde inhibits the formation of retinoic acid from retinal in the rat esophagus.
OBJECTIVE
It has already been demonstrated that the rat esophagus produces retinoic acid from retinol. In this study, this process is further characterized and the effect of acetaldehyde examined to elucidate the possible mechanisms behind the epidemiological evidence that the incidence of esophageal cancer is higher in alcoholics.


METHODS
Rat esophageal samples were incubated with all-trans retinal and newly formed all-trans retinoic acid (ATRA) was quantified using high-performance liquid chromatography (HPLC). Furthermore, beta-nicotinamide adenine dinucleotide (NAD)-dependent acetaldehyde oxidation by the rat esophagus was examined by tracing NAD reduction using a spectrophotometer.


RESULTS
Rat esophageal samples produced ATRA from all-trans retinal in a NAD-dependent manner and the potential was significantly attenuated by phenetyl isothiocynate, an ALDH inhibitor, or acetaldehyde depending on the concentration used. Rat esophageal samples also oxidized acetaldehyde of various concentrations NAD dependently. The ATRA formation potential that was temporarily inhibited by acetaldehyde was recovered to the control level by dialysis when the specimen was incubated with up to 50 microM of acetaldehyde.


CONCLUSIONS
The rat esophagus produces retinoic acid from retinal. An ALDH isoform(s) is responsible for this process and physiological concentration of acetaldehyde hampers the process, probably in a competitive manner. Since the disturbance of retinoic acid supply has been implicated in carcinogenicity, this finding may, at least in part, explain the high incidence of esophageal cancer in alcoholics, especially in those with inactive ALDH 2 whose blood acetaldehyde levels become higher than those with active ALDH 2.
Shiraishi-Yokoyama
Haruko
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Yokoyama
Hirokazu
H
Matsumoto
Michinaga
M
Imaeda
Hiroyuki
H
Hibi
Toshifumi
T
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D012172:Retinaldehyde / Q000378:metabolism*; D013053:Spectrophotometry; D014212:Tretinoin / Q000378:metabolism*
D009243:NAD; D014212:Tretinoin; D000079:Acetaldehyde; D012172:Retinaldehyde