Oxidation of ethanol to acetaldehyde and free radicals by rat testicular microsomes.
A large number of epidemiological studies evidencing that excessive alcohol consumption is associated with impaired testosterone production and testicular atrophy are available in the literature. One hypothesis to explain the deleterious action of alcohol involves the in situ biotransformation to acetaldehyde, but it strongly suggests the need to learn more about the enzymatic processes governing alcohol metabolism to acetaldehyde in different cellular fractions since limited information is available in the literature. In this article we report studies on the metabolic conversion of alcohol to acetaldehyde and to 1-hydroxyethyl radicals in rat testicular microsomal fractions. The oxidation of ethanol to acetaldehyde in rat testes microsomal fraction was mostly of enzymatic nature and strongly dependent on the presence of NADPH and oxygen. Several compounds were able to significantly decrease the production of acetaldehyde: SKF 525A; diethyldithiocarbamate; esculetin; gossypol; curcumin; quercetin; dapsone; and diphenyleneiodonium. Microsomal preparations in the presence of NADPH were also able to produce both hydroxyl and 1-hydroxyethyl free radicals. Their generation was modulated by the presence of diphenyleneiodonium, gossypol, and deferoxamine. Results show that rat microsomal fractions are able to metabolize alcohol to deleterious chemicals, such as acetaldehyde and free radicals, that may be involved in ethanol toxic effects. Enzymes involved could include CYP2E1, P450 reductase, and other enzymes having lipoxygenase- /peroxidase-like behavior.
Quintans
Leandro N
LN
Centro de Investigaciones Toxicológicas (CEITOX) - CITEFA/CONICET, J.B. de La Salle 4397, B1603ALO Villa Martelli, Buenos Aires, Argentina.
Castro
Gerardo D
GD
Castro
José A
JA
D000079:Acetaldehyde / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D000431:Ethanol / Q000493:pharmacokinetics*; D005609:Free Radicals / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000166:cytology / Q000378:metabolism*
D005609:Free Radicals; D000431:Ethanol; D000079:Acetaldehyde