The biological role of D-glucaric acid and its derivatives: Potential use in medicine

被引:0
|
作者
Zoltaszek, Robert [2 ]
Hanausek, Margaret [2 ]
Kilianska, Zofia M. [1 ]
Walaszek, Zbigniew [2 ]
机构
[1] Uniwersytet Lodzki, Katedra Cytobiochem, Zaklad Biochem Med, PL-90237 Lodz, Poland
[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA
来源
POSTEPY HIGIENY I MEDYCYNY DOSWIADCZALNEJ | 2008年 / 62卷
关键词
D-glucaric acid; D-glucaro-1,4-lactone; beta-glucuronidase; cancers; inflammation; apoptosis; oxidative stress;
D O I
暂无
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
D-glucaric acid is a natural non-toxic compound produced in small amounts by mammals, including humans. In mammals, D-glucaric acid and D-glucaro-1,4-lactone are end-products of the D-glucuronic acid pathway. The enzyme D-glucuronolactone dehydrogenase has been found to be responsible for the oxidation of the lactone of D-glucuronic acid to D-glucaro-1,4;6,3-dilactone. This dilactone hydrolyzes spontaneously in aqueous solution to D-glucaro-1,4-lactone, a potent glucuronidase inhibitor. D-glucaric acid is also found in many fruits and vegetables, with the highest concentrations found in grapefruits, apples, oranges, and cruciferous vegetables. beta-glucuronidase is present in the circulation and probably all vertebrate tissues and is capable of hydrolyzing glucuronide conjugates. This enzyme is also produced by colonic microflora. Elevated beta-glucuronidase activity is associated with an increased risk for various cancers, particularly hormone-dependent cancers such as breast and prostate cancer. D-glucaro-1,4-lactone increases detoxification of carcinogens and tumor promoters by inhibiting beta-glucuronidase and preventing the hydrolysis of their glucuronides. D-glucaro-1,4-lactone was found to be formed from supplemented D-glucarate salt in the stomach and it is absorbed from the intestinal track, transported with the blood to different internal organs, and excreted in urine and, to a lesser extent, in bile. D-glucaro-1,4-lactone and its precursors exert their anticancer action in part through alterations in steroidogenesis accompanied by changes in the hormonal environment and proliferative status of the target organs. D-glucarates not only suppress cell proliferation and inflammation, but also induce apoptosis. By supplementing D-glucarates, one can favor the body's natural defense mechanism for eliminating carcinogens and tumor promoters and their effects.
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页码:451 / 462
页数:12
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