INHIBITORY EFFECTS OF SOME PLANT POLYPHENOLS ON THE RAT MAMMARY MICROSOMAL BIOACTIVATION OF ETHANOL TO ACETALDEHYDE

J.A. CASTRO; M.E. MACIEL; G.D. CASTRO

Barcelona

Congreso; XII International Congress of Toxicology; 2010

International Union of Toxicology - Asociación Española de Toxicología

We previously reported the presence of a XOR-mediated cytosolic pathway of ethanol oxidation in rat mammary tissue and that it could be effectively inhibited by several plant polyphenols and by folic acid. Further work also showed that the microsomal fraction also oxidizes ethanol to acetaldehyde, depending on the presence of NADPH and oxygen but not inhibited by carbon monoxide or SKF 525A, but was strongly inhibited by diphenyleneiodonium, a known inhibitor of NADPH oxidase, and by nordihydroguaiaretic acid, an inhibitor of lipoxygenases. This led us to suggest that both enzymes could be involved. In the present studies several plant polyphenols having inhibitory effects on lipoxygenases and of antioxidant nature were tested as potential inhibitors of the rat mammary tissue microsomal pathway of ethanol oxidation to acetaldehyde. We included in the present screening study thirty two polyphenols having ready availability and that were also tested against the rat mammary tissue cytosolic metabolism of ethanol to acetaldehyde. Several polyphenols were also able to inhibit the microsomal ethanol oxidation at concentrations as low was 10-50 micromolar. The results of these screening experiments suggest the potential of several plant polyphenols to prevent in vivo production and accumulation of mutagenic-carcinogenic acetaldehyde in mammary tissue. Supported by ANPCyT (PICT 2004) and CONICET (PIP 5158).