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大鼠腹侧前列腺中黄嘌呤氧化酶介导乙醛代谢为乙酰基自由基。

Rat ventral prostate xanthine oxidase-mediated metabolism of acetaldehyde to acetyl radical.

作者信息

Castro G D, Costantini M H, Castro J A

机构信息

Centro de Investigaciones Toxicológicas (CEITOX-CITEFA/CONICET), Buenos Aires, Argentina.

出版信息

Hum Exp Toxicol. 2009 Apr;28(4):203-8. doi: 10.1177/0960327109105406.

Abstract

Alcohol drinking is known to lead to deleterious effects on prostate epithelial cells from humans and experimental animals. The understanding of the mechanisms underlying these effects is relevant to intraprostatic ethanol treatment of benign prostatic hyperplasia and to shed some light into the conflictive results linking alcohol consumption to prostate cancer. In previous studies, we provided evidence about the presence in the rat ventral prostate of cytosolic and microsomal metabolic pathways of ethanol to acetaldehyde and 1-hydroxyethyl radical and about the low levels of alcohol dehydrogenase and aldehyde dehydrogenase. Acetaldehyde accumulation in prostate tissue and oxidative stress promotion were also observed. In this study, we report that in the ventral prostate cytosolic fraction, xanthine oxidoreductase is able to metabolize acetaldehyde to acetyl radical. The identification of the acetyl was performed by GC-MS of the silylated acetyl-PBN adduct. Reference adduct was generated chemically. Formation of acetyl was also observed using pure xanthine oxidase. The generation of acetyl by the prostate cytosol was inhibited by allopurinol, oxypurinol, diphenyleneiodonium chloride, folate, and ellagic acid. Results suggest that metabolism of ethanol to acetaldehyde and to 1-hydroxyethyl and acetyl radicals could be involved in the deleterious effects of alcohol drinking on prostate epithelial cells.

摘要

众所周知,饮酒会对人类和实验动物的前列腺上皮细胞产生有害影响。了解这些影响背后的机制,对于前列腺内乙醇治疗良性前列腺增生以及阐明饮酒与前列腺癌之间相互矛盾的研究结果具有重要意义。在先前的研究中,我们提供了证据,证明大鼠腹侧前列腺中存在将乙醇代谢为乙醛和1-羟乙基自由基的胞质和微粒体代谢途径,以及低水平的乙醇脱氢酶和乙醛脱氢酶。还观察到前列腺组织中乙醛的积累和氧化应激的促进。在本研究中,我们报告在腹侧前列腺胞质部分,黄嘌呤氧化还原酶能够将乙醛代谢为乙酰自由基。通过硅烷化乙酰-PBN加合物的气相色谱-质谱法鉴定乙酰基。参考加合物通过化学方法生成。使用纯黄嘌呤氧化酶也观察到了乙酰基的形成。别嘌呤醇、氧嘌呤醇、二苯基碘鎓氯化物、叶酸和鞣花酸抑制了前列腺细胞质中乙酰基的生成。结果表明,乙醇代谢为乙醛、1-羟乙基和乙酰自由基可能与饮酒对前列腺上皮细胞的有害影响有关。

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