Rat ventral prostate xanthine oxidase-mediated metabolism of acetaldehyde to acetyl radical.
Alcohol drinking is known to lead to deleterious effects on prostate epithelial cells from humans and experimental animals. The understanding of the mechanisms underlying these effects is relevant to intraprostatic ethanol treatment of benign prostatic hyperplasia and to shed some light into the conflictive results linking alcohol consumption to prostate cancer. In previous studies, we provided evidence about the presence in the rat ventral prostate of cytosolic and microsomal metabolic pathways of ethanol to acetaldehyde and 1-hydroxyethyl radical and about the low levels of alcohol dehydrogenase and aldehyde dehydrogenase. Acetaldehyde accumulation in prostate tissue and oxidative stress promotion were also observed. In this study, we report that in the ventral prostate cytosolic fraction, xanthine oxidoreductase is able to metabolize acetaldehyde to acetyl radical. The identification of the acetyl was performed by GC-MS of the silylated acetyl-PBN adduct. Reference adduct was generated chemically. Formation of acetyl was also observed using pure xanthine oxidase. The generation of acetyl by the prostate cytosol was inhibited by allopurinol, oxypurinol, diphenyleneiodonium chloride, folate, and ellagic acid. Results suggest that metabolism of ethanol to acetaldehyde and to 1-hydroxyethyl and acetyl radicals could be involved in the deleterious effects of alcohol drinking on prostate epithelial cells.
Castro
G D
GD
Centro de Investigaciones Toxicológicas (CEITOX-CITEFA/CONICET), Buenos Aires, Argentina. gcastro@citefa.gov.ar
Costantini
M H
MH
Castro
J A
JA
D000079:Acetaldehyde / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006861:Hydrogen Peroxide; D007501:Iron; D008297:Male; D008892:Milk / Q000201:enzymology; D009249:NADP / Q000378:metabolism; D011467:Prostate / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D014969:Xanthine Oxidase / Q000378:metabolism*
C045076:Fenton's reagent; D005609:Free Radicals; D013113:Spin Labels; D005182:Flavin-Adenine Dinucleotide; D009249:NADP; D006861:Hydrogen Peroxide; D007501:Iron; D014969:Xanthine Oxidase; D000079:Acetaldehyde