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
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.