Alcohol drinking-promoted acetaldehyde accumulation and oxidative stress in rat testes

G.D. CASTRO; L.N. QUINTANS; F. BIETTO; M.I. DÍAZ GÓMEZ; J.A. CASTRO

Washington DC

Congreso; Society of Toxicology Annual Meeting & ToxExpo; 2011

Society of Toxicology

Excessive alcohol consumption is associated with impaired testosterone production and testicular atrophy. Similar findings were observed in in vitro studies on the testosterone production by isolated testes, being acetaldehyde (AC) more potent than alcohol in suppressing testosterone release. In previous studies we reported that rat testicular microsomes were able to bioactivate ethanol to AC, 1-hydroxyethyl and hydroxyl radicals. Now we report that after a single dose of ethanol (3.8 gr/kg, ig.), AC accumulates in testicular tissue for prolonged periods of time (about 9 hours). Comparison against alcohol or AC concentrations in blood and liver tissue up to 24 hours suggests that AC generation in situ is determinant for this cumulative effect. We also observed that testicular cytosolic ADh, xanthine oxidase and AldDh activities were very low or undetectable by histochemical procedures. Six hours after that single dose of ethanol the testicular levels of lipids hydroperoxides (xylenol orange method) were significantly increased. Similar observations were made in testes from animals receiving a standard Lieber and De Carli diet during 28 days. We also tested twenty four polyphenols having known antioxidant properties against the NADPH dependent and the NADPH non-dependent microsomal metabolism of alcohol to AC. Some of them exhibit significant inhibitory effects at low concentrations (10-50 micromolar) on both metabolic processes. Results suggest that in situ microsomal metabolism of alcohol to AC and the low AldDh activity present at the testicular tissue might be involved in the AC accumulation observed, and that our previously reported alcohol-promoted generation of 1-hydroxyethyl and hydroxyl radicals might initiate the lipid peroxidation process leading to production of the lipid hydroperoxides detected in vivo. Ability of polyphenols to inhibit these microsomal pathways of alcohol metabolism at low concentrations suggest preventive effects of them against alcohol induced testicular damage and reproductive impairment, that remain to be established.