Influences of dietary soy isoflavones on metabolism but not nociception and stress hormone responses in ovariectomized female rats

BACKGROUND: Isoflavones, the most abundant phytoestrogens in soy foods, are structurally similar to 17beta-estradiol. Few studies have examined the nociception and stress hormone responses after consumption of soy isoflavones. METHODS: In this study, ovariectomized (OVX) female Long-Evans rats were fed either an isoflavone-rich diet (Phyto-600) or an isoflavone-free diet (Phyto-free). We examined the effects of soy isoflavones on metabolism by measuring body weights, food/water intake, adipose tissue weights as well as serum leptin levels. Also, circulating isoflavone levels were quantified. During chemically induced estrous, nociceptive thresholds were recorded. Then, the animals were subjected to a stressor and stress hormone levels were quantified. RESULTS: Body weights were significantly lower in Phyto-600 fed rats compared to Phyto-free values within one week and during long-term consumption of soy isoflavones. Correspondingly, Phyto-600 fed animals displayed significantly less adipose deposition and lower serum leptin levels than Phyto-free values. However, rats on the Phyto-600 diet displayed greater food/water intake compared to Phyto-free levels. No changes in thermal pain threshold or stress hormone levels (ACTH and corticosterone) were observed after activation of the hypothalamic-pituitary-adrenal (HPA) stress axis. CONCLUSION: In summary, these data show that consumption of soy isoflavones 1) increases metabolism, demonstrated by significantly decreased body weights, adipose tissue deposition and leptin levels, but 2) does not alter nociception or stress hormone responses, as indexed by thermal pain threshold, serum corticosterone and ACTH levels in chemically-induced estrous OVX rats

Timing of supplementation of selenium and isoflavones determines prostate cancer risk factor reduction in rats

<p>Abstract</p> <p>Background</p> <p>High dietary intake of selenium or isoflavones reduces risk factors for prostate cancer. We tested whether combined supplementation of these two dietary components would reduce prostate cancer risk factors in rats more than supplementation of each component individually.</p> <p>Methods</p> <p>Male Noble rat pups were exposed from conception to diets containing an adequate (0.33–0.45 mg/kg diet) or high (3.33–3.45 mg/kg) concentration of selenium as Se-methylselenocysteine and a low (10 mg/kg) or high (600 mg/kg) level of isoflavones in a 2 × 2 factorial design. Pups consumed their respective diets until sacrifice at 35, 100, or 200 days. Male Noble rat breeders, whose exposure to the diets began after puberty, were sacrificed at 336 days. Rats were weighed biweekly. Blood was collected at the time of sacrifice and body fat and prostates were dissected and weighed. Serum levels of leptin, IGF-1, and testosterone were determined using ELISA kits. Serum levels of isoflavones were assayed by GC/MS. Liver activity of selenium-dependent glutathione peroxidase 1 was measured as an indicator of selenium status.</p> <p>Results</p> <p>Serum isoflavone concentrations were nearly 100-fold higher at 35 days of age (1187.1 vs. 14.4 ng/mL, mean ± SD) in pups fed the high vs. low isoflavone diets, and remained so at 100 and 200 days, and in breeders. There were no dietary differences in liver glutathione peroxidase activity in pups or breeders. High isoflavone intake significantly (p = 0.001–0.047) reduced body weight in rat pups from 35 days onward, but not in breeders. Body fat and leptin were likewise significantly reduced by high isoflavones in pups while effects in breeders were less pronounced but still significant. High intake of Se and isoflavones each decreased serum IGF-1 in pups at 100 and 200 days, but not in breeders. No consistent dietary effects were observed on serum testosterone or relative weights of prostates. In pups, the combination of high isoflavones and high selenium produced the lowest weight gain, the lowest serum leptin, and the lowest serum IGF-1 concentrations of all four diets.</p> <p>Conclusion</p> <p>Combined intake of high selenium and high isoflavones may achieve greater chemopreventive effects than either compound individually. The timing of supplementation may determine the significance of its effects.</p

Timing of supplementation of selenium and isoflavones determines prostate cancer risk factor reduction in rats

<p>Abstract</p> <p>Background</p> <p>High dietary intake of selenium or isoflavones reduces risk factors for prostate cancer. We tested whether combined supplementation of these two dietary components would reduce prostate cancer risk factors in rats more than supplementation of each component individually.</p> <p>Methods</p> <p>Male Noble rat pups were exposed from conception to diets containing an adequate (0.33–0.45 mg/kg diet) or high (3.33–3.45 mg/kg) concentration of selenium as Se-methylselenocysteine and a low (10 mg/kg) or high (600 mg/kg) level of isoflavones in a 2 × 2 factorial design. Pups consumed their respective diets until sacrifice at 35, 100, or 200 days. Male Noble rat breeders, whose exposure to the diets began after puberty, were sacrificed at 336 days. Rats were weighed biweekly. Blood was collected at the time of sacrifice and body fat and prostates were dissected and weighed. Serum levels of leptin, IGF-1, and testosterone were determined using ELISA kits. Serum levels of isoflavones were assayed by GC/MS. Liver activity of selenium-dependent glutathione peroxidase 1 was measured as an indicator of selenium status.</p> <p>Results</p> <p>Serum isoflavone concentrations were nearly 100-fold higher at 35 days of age (1187.1 vs. 14.4 ng/mL, mean ± SD) in pups fed the high vs. low isoflavone diets, and remained so at 100 and 200 days, and in breeders. There were no dietary differences in liver glutathione peroxidase activity in pups or breeders. High isoflavone intake significantly (p = 0.001–0.047) reduced body weight in rat pups from 35 days onward, but not in breeders. Body fat and leptin were likewise significantly reduced by high isoflavones in pups while effects in breeders were less pronounced but still significant. High intake of Se and isoflavones each decreased serum IGF-1 in pups at 100 and 200 days, but not in breeders. No consistent dietary effects were observed on serum testosterone or relative weights of prostates. In pups, the combination of high isoflavones and high selenium produced the lowest weight gain, the lowest serum leptin, and the lowest serum IGF-1 concentrations of all four diets.</p> <p>Conclusion</p> <p>Combined intake of high selenium and high isoflavones may achieve greater chemopreventive effects than either compound individually. The timing of supplementation may determine the significance of its effects.</p

Diets high in selenium and isoflavones decrease androgen-regulated gene expression in healthy rat dorsolateral prostate

<p>Abstract</p> <p>Background</p> <p>High dietary intake of selenium or soybean isoflavones reduces prostate cancer risk. These components each affect androgen-regulated gene expression. The objective of this work was to determine the combined effects of selenium and isoflavones on androgen-regulated gene expression in rat prostate.</p> <p>Methods</p> <p>Male Noble rats were exposed from conception until 200 days of age to diets containing an adequate (0.33-0.45 mg/kg diet) or high (3.33-3.45 mg/kg) concentration of selenium as Se-methylselenocysteine and a low (10 mg/kg) or high (600 mg/kg) level of isoflavones in a 2 × 2 factorial design. Gene expression in the dorsolateral prostate was determined for the androgen receptor, for androgen-regulated genes, and for Akr1c9, whose product catalyzes the reduction of dihydrotestosterone to 5alpha-androstane-3alpha, 17beta-diol. Activity of hepatic glutathione peroxidise 1 and of prostatic 5alpha reductase were also assayed.</p> <p>Results</p> <p>There were no differences due to diet in activity of liver glutathione peroxidase activity. Total activity of 5alpha reductase in prostate was significantly lower (<it>p </it>= 0.007) in rats fed high selenium/high isoflavones than in rats consuming adequate selenium/low isoflavones. High selenium intake reduced expression of the androgen receptor, Dhcr24 (24-dehydrocholesterol reductase), and Abcc4 (ATP-binding cassette sub-family C member 4). High isoflavone intake decreased expression of Facl3 (fatty acid CoA ligase 3), Gucy1a3 (guanylate cyclase alpha 3), and Akr1c9. For Abcc4 the combination of high selenium/high isoflavones had a greater inhibitory effect than either treatment alone. The effects of selenium on gene expression were always in the direction of chemoprevention</p> <p>Conclusion</p> <p>These results suggest that combined intake of high selenium and high isoflavones may achieve a greater chemopreventive effect than either compound supplemented individually.</p

Visual spatial memory is enhanced in female rats (but inhibited in males) by dietary soy phytoestrogens

BACKGROUND: In learning and memory tasks, requiring visual spatial memory (VSM), males exhibit superior performance to females (a difference attributed to the hormonal influence of estrogen). This study examined the influence of phytoestrogens (estrogen-like plant compounds) on VSM, utilizing radial arm-maze methods to examine varying aspects of memory. Additionally, brain phytoestrogen, calbindin (CALB), and cyclooxygenase-2 (COX-2) levels were determined. RESULTS: Female rats receiving lifelong exposure to a high-phytoestrogen containing diet (Phyto-600) acquired the maze faster than females fed a phytoestrogen-free diet (Phyto-free); in males the opposite diet effect was identified. In a separate experiment, at 80 days-of-age, animals fed the Phyto-600 diet lifelong either remained on the Phyto-600 or were changed to the Phyto-free diet until 120 days-of-age. Following the diet change Phyto-600 females outperformed females switched to the Phyto-free diet, while in males the opposite diet effect was identified. Furthermore, males fed the Phyto-600 diet had significantly higher phytoestrogen concentrations in a number of brain regions (frontal cortex, amygdala & cerebellum); in frontal cortex, expression of CALB (a neuroprotective calcium-binding protein) decreased while COX-2 (an inducible inflammatory factor prevalent in Alzheimer's disease) increased. CONCLUSIONS: Results suggest that dietary phytoestrogens significantly sex-reversed the normal sexually dimorphic expression of VSM. Specifically, in tasks requiring the use of reference, but not working, memory, VSM was enhanced in females fed the Phyto-600 diet, whereas, in males VSM was inhibited by the same diet. These findings suggest that dietary soy derived phytoestrogens can influence learning and memory and alter the expression of proteins involved in neural protection and inflammation in rats

A combination of mutations in AKR1D1 and SKIV2L in a family with severe infantile liver disease.

Infantile cholestatic diseases can be caused by mutations in a number of genes involved in different hepatocyte molecular pathways. Whilst some of the essential pathways have a well understood function, such as bile biosynthesis and transport, the role of the others is not known. Here we report the findings of a clinical, biochemical and molecular study of a family with three patients affected with a severe infantile cholestatic disease. A novel homozygous frameshift germline mutation (c.587delG) in the AKR1D1 gene; which encodes the enzyme Δ 4-3-oxosteroid 5β-reductase that is required for synthesis of primary bile acids and is crucial for establishment of normal bile flow, was found in all 3 patients. Although the initial bile acid analysis was inconclusive, subsequent testing confirmed the diagnosis of a bile acid biogenesis disorder. An additional novel homozygous frameshift mutation (c.3391delC) was detected in SKIV2L in one of the patients. SKIV2L encodes a homologue of a yeast ski2 protein proposed to be involved in RNA processing and mutations in SKIV2L were recently described in patients with Tricohepatoenteric syndrome (THES). A combination of autozygosity mapping and whole-exome-sequencing allowed the identification of causal mutations in this family with a complex liver phenotype. Although the initial 2 affected cousins died in the first year of life, accurate diagnosis and management of the youngest patient led to successful treatment of the liver disease and disease-free survival.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Global gene expression profile progression in Gaucher disease mouse models

<p>Abstract</p> <p>Background</p> <p>Gaucher disease is caused by defective glucocerebrosidase activity and the consequent accumulation of glucosylceramide. The pathogenic pathways resulting from lipid laden macrophages (Gaucher cells) in visceral organs and their abnormal functions are obscure.</p> <p>Results</p> <p>To elucidate this pathogenic pathway, developmental global gene expression analyses were conducted in distinct <it>Gba1 </it>point-mutated mice (V394L/V394L and D409 V/null). About 0.9 to 3% of genes had altered expression patterns (≥ ± 1.8 fold change), representing several categories, but particularly macrophage activation and immune response genes. Time course analyses (12 to 28 wk) of INFγ-regulated pro-inflammatory (13) and IL-4-regulated anti-inflammatory (11) cytokine/mediator networks showed tissue differential profiles in the lung and liver of the <it>Gba1 </it>mutant mice, implying that the lipid-storage macrophages were not functionally inert. The time course alterations of the INFγ and IL-4 pathways were similar, but varied in degree in these tissues and with the <it>Gba1 </it>mutation.</p> <p>Conclusions</p> <p>Biochemical and pathological analyses demonstrated direct relationships between the degree of tissue glucosylceramides and the gene expression profile alterations. These analyses implicate IFNγ-regulated pro-inflammatory and IL-4-regulated anti-inflammatory networks in differential disease progression with implications for understanding the Gaucher disease course and pathophysiology.</p