METABOLISM, UPTAKE, AND EXCRETION OF A D-GLUCARIC ACID SALT AND ITS POTENTIAL USE IN CANCER PREVENTION

Citation
Z. Walaszek et al., METABOLISM, UPTAKE, AND EXCRETION OF A D-GLUCARIC ACID SALT AND ITS POTENTIAL USE IN CANCER PREVENTION, Cancer detection and prevention, 21(2), 1997, pp. 178-190
Citations number
23
Categorie Soggetti
Oncology
ISSN journal
0361090X
Volume
21
Issue
2
Year of publication
1997
Pages
178 - 190
Database
ISI
SICI code
0361-090X(1997)21:2<178:MUAEOA>2.0.ZU;2-N
Abstract
D-Glucaric acid (GA) is a nontoxic, natural compound. One of its deriv atives is the potent beta-glucuronidase inhibitor D-glucaro-1,4-lacton e (1,4-GL). The goal of this study was to demonstrate the in vivo form ation of 1,4-GL from a D-glucarate salt and determine its metabolism, uptake by selected organs, and excretion following oral administration of potassium hydrogen D-[C-14]glucarate to male and female Sprague-Da wley rats. 1,4-GL increases detoxification of carcinogens and tumor pr omoters/progressor, by inhibiting beta-glucuronidase and preventing hy drolysis of their glucuronides. 1,4-GL and its precursors, such as pot assium hydrogen D-glucarate and calcium D-glucarate, may exert their a nticancer action, in part, through alterations in steroidogenesis acco mpanied by changes in the hormonal environment and the proliferative s tatus of the target organ. Thus, GA derivatives may be useful as new o r adjuvant cancer preventive and therapeutic agents. In our study. 1,4 -GL was found to be formed from the D-glucarate salt in the stomach of rats. It was apparently absorbed from the gastrointestinal tract. tra nsported with the blood to different internal organs, and excreted in the urine and to a lesser extent in bile. There were no significant di fferences in the metabolism of PHG between male and female rats. Thus, formation of 1,4-GL from D-glucaric acid derivatives mag be prerequis ite for their inhibition of chemical carcinogenesis in rodents and pre vention of breast, prostate, and colon cancer in humans.