Toxicological Sciences 65, 228-238 (2002)
Copyright © 2002 by the Society of Toxicology
REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY |
Daidzein: Bioavailability, Potential for Reproductive Toxicity, and Breast Cancer Chemoprevention in Female Rats
,1
* Department of Pharmacology and Toxicology, 101C Volker Hall, 1670 University Boulevard, Birmingham, Alabama 35294;
UAB Comprehensive Cancer Center, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, Alabama 35294; and
Department of Pathology, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, Alabama 35294
Soy products containing phytoestrogens have received much attention as dietary components to promote better health. Daidzein, an isoflavone and phytoestrogen component of soy, was investigated for its potential to alter fertility and cause developmental toxicity to the reproductive tract in female rats, for chemoprevention to the mammary gland, and to study its bioavailability. Diets containing 0 mg, 250 mg (low dose), and 1000 mg (high dose) daidzein/kg feed were fed to virgin female rats, starting 2 weeks prior to breeding and continued until the offspring were 50 days postpartum. The serum daidzein concentrations in adult female rats fed the low and high daidzein-containing diets were determined to be 6- and 13-fold higher than serum daidzein concentrations of Asians eating a traditional diet high in soy. Both daidzein doses had no significant effect on fertility, numbers of male and female offspring, and anogenital distances. The high, but not the low, daidzein dose resulted in reduced body weight, a fact that may be explained by reduced feed consumption. Circulating progesterone, but not estrogen, levels were statistically reduced with the high, but not low daidzein-containing diet. Both daidzein doses resulted in slight, but not significant, decreases in ovarian and uterine weights, and mammary gland size. Histomorphological analysis of the reproductive tracts of female offspring 50 days of age exposed perinatally to daidzein did not reveal any pathology in the vaginal, uterine, ovarian, and mammary tissues. Perinatal exposure of female offspring to 250 mg daidzein/kg diet did not alter mammary gland development or ontogeny of chemically induced mammary tumors in rats treated with dimethylbenz(a)anthracene on day 50. With the low dietary daidzein dose, total equol (major metabolite) and daidzein concentrations in the blood of pregnant females, 7-day-old, 21-day-old, and 50-day-old female offspring were 529 and 303 nM, 163 and 982 nM, 1188 and 1359 nM, and 3826 and 630 nM, respectively. With the high daidzein diet, equol and daidzein concentrations in the blood of pregnant females, 7-day-old, 21-day-old, and 50-day-old female offspring were 4462 and 407 nM, 1013 and 3841 nM, 6472 and 3308 nM, and 7228 and 1430 nM, respectively. Eighty-nine to 99% of daidzein and equol were in the conjugated form. In the 21-day-old postconceptus exposed to the low and high daidzein diets, total equol and daidzein blood concentrations were 59 and 34 nM, and 358 and 132 nM, respectively. Virtually all of the daidzein in the milk of 7-day-old rats exposed to the low and high daidzein-containing diet were unconjugated, 2.6 µM and 7.3 µM, respectively. Total milk equol concentrations were 654 nM and 3.8 µM, of which 94% and 44% were unconjugated. In mammary glands of 7-day-old offspring exposed to 250 mg daidzein/kg diet, total daidzein concentrations were 407 nM (98% aglycone). We conclude that supraphysiological concentrations of daidzein administered via the diet did not cause significant toxicity to the female reproductive tract or provide a protective effect against chemically induced mammary cancer.
Key Words: daidzein; phytoestrogen; bioavailability; toxicology.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Mardon, J. Mathey, S. Kati-Coulibaly, C. Puel, M.-J. Davicco, P. Lebecque, M.-N. Horcajada, and V. Coxam Influence of Lifelong Soy Isoflavones Consumption on Bone Mass in the Rat Experimental Biology and Medicine, February 1, 2008; 233(2): 229 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. J. Wang, J. Chen, X. Jia, V. H. Tam, and M. Hu Disposition of Flavonoids via Enteric Recycling: Structural Effects and Lack of Correlations between in Vitro and in Situ Metabolic Properties Drug Metab. Dispos., November 1, 2006; 34(11): 1837 - 1848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Messina, W. McCaskill-Stevens, and J. W. Lampe Addressing the soy and breast cancer relationship: review, commentary, and workshop proceedings. J Natl Cancer Inst, September 20, 2006; 98(18): 1275 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Wood, S. E. Appt, T. B. Clarkson, A. A. Franke, C. J. Lees, D. R. Doerge, and J. M. Cline Effects of High-Dose Soy Isoflavones and Equol on Reproductive Tissues in Female Cynomolgus Monkeys Biol Reprod, September 1, 2006; 75(3): 477 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. H. Ju, J. Fultz, K. F. Allred, D. R. Doerge, and W. G. Helferich Effects of dietary daidzein and its metabolite, equol, at physiological concentrations on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice Carcinogenesis, April 1, 2006; 27(4): 856 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Rowell, D. M. Carpenter, and C. A. Lamartiniere Chemoprevention of Breast Cancer, Proteomic Discovery of Genistein Action in the Rat Mammary Gland J. Nutr., December 1, 2005; 135(12): 2953S - 2959S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Weaver and J. M. K. Cheong Soy Isoflavones and Bone Health: The Relationship Is Still Unclear J. Nutr., May 1, 2005; 135(5): 1243 - 1247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Atkinson, C. L. Frankenfeld, and J. W. Lampe Gut Bacterial Metabolism of the Soy Isoflavone Daidzein: Exploring the Relevance to Human Health Experimental Biology and Medicine, March 1, 2005; 230(3): 155 - 170. [Abstract] [Full Text] [PDF]
|
|