Ethanol single dose provoked acetaldehyde accumulation and oxidative stress potential in rat mammary tissue. A consequence of a limited breast ability for detoxication of alcohol

CASTRO GD; DELGADO DE LAYÑO AM; FANELLI SL; MACIEL ME; DÍAZ GÓMEZ MI; CASTRO JA.

Cavtat/Dubrovnik,

Congreso; EUROTOX 2006/.CTDC Congress. 43th Congress of European Societies of Toxicology. 6th Congress of Toxicology in Developing Countries; 2006

European Societies of Toxicology (EUROTOX)

In previous studies from our laboratory the presence of several pathways of metabolic activation of ethanol to acetaldehyde and hydroxyl free radicals as well as the promotion of  oxidativestress were reported. Other laboratories also reported the presence of type I alcohol dehydrogenase and of CYP2E1 and a limited presence of aldehyde dehydrogenase. In the present studies we tested the possibility that after a single dose of alcohol, acetaldehyde accumulated in mammary tissue to reach concentrations higher than in blood. Three different doses of alcohol were tested and acetaldehyde concentrations in breast, liver and blood were measured at times ranging from 1 to 24 hours. We also determined alcohol dehydrogenase; aldehyde dehydrogenase and p-nitrophenol hydroxylase activities.  Oxidative stress induced hydroperoxyde formation studies, as determined the xylenol orange procedure, are in course for each dose at different times of exposure and at present led to positive results at some times for the highest dose tested. The obtained results showed that acetaldehyde concentrations at the three alcohol doses tested (low, medium and high) were always higher than in blood. Peak concentrations of acetaldehyde in liver, while higher than those in breast, appeared to decrease to blood levels following a similar time sequence. Limited activities of alcohol dehydrogenase and aldehyde dehydrogenase in mammary tissue were observed. The microsomal CYP2E1-mediated p-nitrophenol hydroxylase in mammary tissue was several times smaller than in liver. In summary, results suggest that the mutagen acetaldehyde, either formed in situ or, even in small amounts, continuously arriving via blood, tends to accumulate in mammary tissue as a consequence of a limited capacity of it for detoxication. During the period of alcohol exposure, the GSH levels in mammary tissue were not decreased. Supported by grants from ANPCyT-SECyT (PICT 05-6045) and from UNSAM (PIB S05/03).