Centro de Investigaciones Toxicológicas (CEITOX-CITEFA/ CONICET), J B de La Salle 4397, Villa Martelli, Buenos Aires, Argentina.
Hum Exp Toxicol. 2011 Jul;30(7):656-64. doi: 10.1177/0960327110377522. Epub 2010 Nov 26.
We previously reported that the microsomal fraction from rat mammary tissue is able to oxidize ethanol to acetaldehyde, a mutagenic-carcinogenic metabolite, depending on the presence of NADPH and oxygen but not inhibited by carbon monoxide or other cytochrome P450 inhibitors. The process 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. With the purpose of identifying natural compounds present in food with the ability to decrease the production of acetaldehyde in mammary tissue, 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. We included in the present screening study 32 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 μM. The results of these screening experiments suggest the potential of several plant polyphenols to prevent in vivo production and accumulation of acetaldehyde in mammary tissue.
我们之前曾报道，大鼠乳腺组织的微粒体部分能够将乙醇氧化为具有诱变致癌作用的代谢物乙醛，这一过程依赖于 NADPH 和氧的存在，而不受一氧化碳或其他细胞色素 P450 抑制剂的抑制。二苯并碘onium 是 NADPH 氧化酶的一种已知抑制剂，以及 nordihydroguaiaretic 酸（脂氧合酶抑制剂）均可强烈抑制这一过程。这使我们推测这两种酶都可能参与其中。为了鉴定食物中存在的具有降低乳腺组织乙醛生成能力的天然化合物，在目前的研究中，我们测试了几种具有脂氧合酶抑制作用和抗氧化性质的植物多酚，作为大鼠乳腺组织微粒体乙醇氧化途径的潜在抑制剂。我们在本次筛选研究中纳入了 32 种多酚，这些多酚不仅容易获得，而且还针对大鼠乳腺组织胞质中乙醇向乙醛的代谢进行了测试。一些多酚在低至 10-50 μM 的浓度下也能抑制微粒体乙醇氧化。这些筛选实验的结果表明，几种植物多酚具有预防体内乳腺组织中乙醛生成和积累的潜力。
