AbstractThe individual and combined effects of dietary toasted soybean meal (3.13–25%) and dietary licorice root extract (0.38–3.0%) on selected liver and intestinal enzyme levels and on clinical chemistry and histopathological parameters were evaluated on male F344 rats. All parameters were measured one and three months after the 50‐day‐old rats were started on the diets. By use of newly developed high‐performance liquid chromatography‐based analytic methods, measurable levels of daidzein (2.67μg/ml) and glycyrrhetinic acid (7.87μg/ml) were detected in the sera of rats on the 25% soybean and 3% licorice diets, respectively. Histopathological evaluations of organs and tissues yielded only nonsignificant strain‐related changes. At all dosages, there were no significant soybean‐or licorice‐related anatomic lesions or hematologic changes. In the clinical biochemistry profile, soybean meal caused moderate but significant dose‐dependent decreases in serum cholesterol and increases in alkaline phosphatase, blood urea nitrogen, and phosphorus, which remained within the normal range. Liver glutathione transferase, catalase, and protein kinase C showed significant inductions (up to 50%) in response to increasing doses of soybean meal and licorice extract, with evidence for only marginal interaction between the two additives. Their effects on the intestinal mucosa were not significant. Ornithine decarboxylase levels, an indicator of promotional activity, were unchanged or repressed by the additives.The favorable effects of up to 25% toasted soybean meal and 3% licorice root extract on the levels of the four enzymes, without unfavorable changes in clinical parameters, might account in part for the chemopreventive activities of these additives. These effects would be in addition to direct inhibitory effects of known components in these additives on these or other enzymes or modulation of hormone activity that is not evaluated in this study.