D-Glucaric acid (GA) is a nontoxic, natural compound. One of its derivatives is the potent
beta-glucuronidase inhibitor D-glucaro-1,4-lactone (1,4-GL). The goal of this study was to demonstrate the in vivo formation 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-[14C]glucarate to male and female Sprague-Dawley rats. 1,4-GL increases detoxification of
carcinogens and
tumor promoters/progressors by inhibiting
beta-glucuronidase and preventing hydrolysis of their
glucuronides. 1,4-GL and its precursors, such as
potassium hydrogen D-glucarate and
calcium D-glucarate, may exert their anticancer action, in part, through alterations in steroidogenesis accompanied by changes in the hormonal environment and the proliferative status of the target organ. Thus, GA derivatives may be useful as new or 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, transported with the blood to different internal organs, and excreted in the urine and to a lesser extent in bile. There were no significant differences in the metabolism of PHG between male and female rats. Thus, formation of 1,4-GL from
D-glucaric acid derivatives may be prerequisite for their inhibition of chemical
carcinogenesis in rodents and prevention of breast, prostate, and
colon cancer in humans.