Age decreased steady-state concentrations of genistein in plasma, liver, and skeletal muscle in Sprague–Dawley rats

https://doi.org/10.1016/j.mad.2005.12.003Get rights and content

Abstract

Soy isoflavones are associated with low incidence of cardiovascular diseases (CVD) and hormone-dependent cancers, but no solid information is available on the relative deposition of isoflavones in the body as a function of age. One-year-old (adult) male Sprague–Dawley rats were fed control diet or one of three high-genistein isoflavone (HGI) diets at a dose of 62, 154, or 308 genistein mg/kg (ppm) diet for 5 weeks; 2-year-old (old) were fed a dose of 154 or 308 ppm. Steady-state genistein concentrations in plasma, liver, and gastrocnemius muscle of the adult rats after 12 h fast revealed a linear dose-dependent manner (P  0.0001). However, there was no such relationship in the old rats. Nevertheless, old rats fed the 308 ppm genistein diet had significantly lower steady-state genistein concentrations in plasma and liver than the adult rats did (P  0.05); but similar genistein concentration in muscle. The results of this study indicate that steady-state genistein concentrations in tissues of adult rats after 12 h fast exhibited a dose-dependent fashion and were diminished in specific tissues by age.

Introduction

Soy has been recognized as one of the healthy components in the Asian diet. Its consumption is associated with lower mortality and morbidity from cardiovascular diseases (CVD) and hormone-dependent cancers (Tikkanen and Adlercreutz, 2000, Adlercreutz, 2002). Isoflavones in soy exhibit a wide range of biological activities, including antioxidant, estrogenic, anti-estrogenic, cholesterol lowering, and anticarcinogenic, all of which may all contribute to such health protective effects (Setchell, 1998, Messina, 1999, Tikkanen and Adlercreutz, 2000).

Bioavailability of isoflavones and subsequent metabolisms via the phase II pathways in humans and animals has been established (Hendrich, 2002). When ingested, genistin and daidzin, β-glycoside conjugates of genistein and daidzein primarily found in foods, were absorbed as aglycones after glucose was hydrolyzed by the action of microbial β-glycosidase (Sfakianos et al., 1997). Genistein and daidzein reached their maximum plasma concentrations in rats after 1 h of an acute administration of glycone forms, and they were excreted after 24 h (Uehara et al., 2001). Confounding factors seem to modulate the extent of bioavailabilities and pharmacokinetics of isoflavones. For example, soy milk led to a higher urinary genistein recovery than did textured vegetable protein in humans (Faughnan et al., 2004), and male rats had a larger maximum plasma genistein concentration than did female rats (Coldham and Sauer, 2000). Recently, Faughnan et al. (2004) proposed the effect of age on isoflavone bioavailability in women; however, they did not observe disparity between postmenopausal and premenopausal women.

Fundamental information on bioavailability, metabolisms, and deposition of isoflavones is crucial to evaluate and understand their bio-efficacy on health prevention and protection. Although gender and food mixture has been shown to affect isoflavone bioavailability, to date, the effect of age on steady-state concentration of isoflavones in tissues is unclear. This study, approved by the Virginia Tech Institutional Review Board, was to investigate whether steady-state concentration of genistein, after 12 h fast, in plasma, liver, and gastrocnemius muscle exhibited a dose-dependent manner in adult Sprague–Dawley rats, and whether age affected these concentrations.

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Animals

Total 32 Sprague–Dawley male rats (1-year old (adult), mean body weight (BW) 499 ± 6 g; 2-year old (old), mean BW 681 ± 5 g) were used in the study after 1-week acclimation with control diet. Twenty-four adult rats were purchased from the Harlan Industries (Indianapolis, IN) before the study, whereas eight old rats from the same vendor were obtained at 1 year of age and kept at the animal facility for another year; hence, were 2 years old at start of study. Both adult and aged rats were each housed

Feed intake, weight gain, and genistein consumption

Genistein diets did not influence feed intake and weight gain in adult (1-year old) and old (2-year old) rats during the 35-day experiment. Overall means of weight gain during experimental period was 0.8 ± 0.1 g/day. Mean feed intake for adult rats in control and 62, 154, and 308 genistein group during the study was 20.4 ± 0.7, 21.1 ± 1.0, 21.7 ± 0.8, 19.8 ± 0.7 g/day, respectively, and for old rats in 154 and 308 genistein group was 21.5 ± 0.6 and 20.1 ± 1.2 g/day, respectively. At the end of study, mean BW of

Discussion

Soy protein consumption lowers the incidence of cardiovascular diseases and specific cancers in Asians (Tikkanen and Adlercreutz, 2000, Adlercreutz, 2002). Each or a combination of many components in soy protein, such as isoflavones, saponins, fiber, and the amino acid composition may contribute to its health benefits. Isoflavones, especially, have drawn a good deal of attention because of their estrogen-like, anticarcinogenic, and antioxidant activities. Numerous studies have demonstrated

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Support was provided by the Virginia Soybean Association.

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