Search

Andropause, the culminating phase of male ageing, is characterized by deregulation of the hypothalamic-pituitarygonadal axis and low circulating free testosterone. The aim of this study was to investigate the immunohistomorphometric characteristics of the pituitary gonadotropic i.e. follicle-stimulating hormone (FSH) and the luteinizing hormone (LH) producing cells after testosterone application in a rat model of the andropause. Middle-aged Wistar rats were divided into orchidectomized (ORX; n=8) and testosterone treated orchidectomized (ORX+T; n=8) groups. Testosterone propionate (5 mg/kg b.m./day) was administered for three weeks, while the ORX group received the vehicle alone. Immunohistochemically stained FSH and LH cells underwent morphometric and optical density-related analysis, while circulating concentrations of the sex steroids were measured by immunoassays. Serum concentrations of testosterone and estradiol were significantly (pi.e. this parameter of FSH and LH cells was significantly (p

International audience; Scope: Flavanols are important polyphenols of the human diet with extensive demonstrations of their beneficial effects on cardiometabolic health. They contribute to preserve health acting on a large range of cellular processes. The underlying mechanisms of action of flavanols are not fully understood but involve a nutrigenomic regulation. Methods and Results: To further capture how the intake of dietary flavanols results in the modulation of gene expression, nutrigenomics data in response to dietary flavanols obtained from animal models of cardiometabolic diseases have been collected and submitted to a bioinformatics analysis. This systematic analysis shows that dietary flavanols modulate a large range of genes mainly involved in endocrine function, fatty acid metabolism, and inflammation. Several regulators of the gene expression have been predicted and include transcription factors, miRNAs and epigenetic factors. Conclusion: This review highlights the complex and multilevel action of dietary flavanols contributing to their strong potential to preserve cardiometabolic health. The identification of the potential molecular mediators and of the flavanol metabolites driving the nutrigenomic response in the target organs is still a pending question which the answer will contribute to optimize the beneficial health effects of dietary bioactives.

In a series of our previous works, we revealed the beneficial effects of applied soy isoflavones (genistein or daidzein) on the wide context of corticosteroidogenesis in vivo, in a rat model of the andropause. Soy isoflavones decreased the circulating levels of pituitary adrenocorticotropic hormone, inhibited aldosterone secretion, as well as corticosterone production and secretion, but stimulated dehydroepiandrosterone secretion, all in andropausal rats. In vitro studies indicate that the mechanism underlying these hormonal changes relies on inhibition of the pituitary tyrosine kinase and adrenocortical 3β-hydroxysteroid dehydrogenase enzymes by soy isoflavones. Although the clinical studies are in their infancy, the opinion is that genistein and daidzein have therapeutic potential for the safe treatment of ageing-caused androgen deprivation and glucocorticoid excess with related metabolic/hemodynamic issues in males. Our accumulated experience and knowledge in the field of biomedical effects of plant polyphenols have provided a platform for potential recommending the agenda to organize and accelerate experimental research aimed at producing the optimal supplementation. We hypothesize that an in vivo approach should first be exploited in the sequence of investigative steps, followed by in vitro studies and synchronously conducted molecular docking analyses. In vivo research, besides establishing the margin of exposure safety or adjustment of the correct polyphenol dose, enables identification and quantification of the metabolites of applied polyphenols in the blood. Subsequent in vitro exploitation of the metabolites and related docking analyses provide clarification of the molecular mechanisms of action of applied polyphenols. Chemical modification of the polyphenol structure or coupling it with nanoparticles might be the next step in optimizing the design of supplementation. Selected, intact or chemically-modified polyphenol molecules should be included in preclinical studies on a more closely-related species, while clinical studies would finally assess the safety and effectiveness of a polyphenol-based remedial strategy. The final supplement represents a product of an appropriate technological process, conducted in accordance with the recommendations derived from the preceding research.

As a major phytoestrogen of soy, genistein effectively prevents bone loss in both humans and rat models of osteoporosis. However, although the bone‐sparing effects of genistein are achieved directly through estrogen receptors, its mode of action on bone by modulation of other endocrine functions is not entirely clear. Thus, thyroid hormones and calcitonin (CT) have an essential influence on bone metabolism. Besides its action on bones, in this study we examined the effect of genistein on the activity of two different endocrine cell populations, thyroid follicular and C‐cells. Fifteen‐month‐old Wistar rats were either bilaterally orchidectomized (Orx) or sham‐operated (SO). Two weeks after surgery, half of the Orx rats were treated chronically with 30 mg kg(−1) b.w. genistein (Orx + G) subcutaneously (s.c.) every day for 3 weeks, while the remaining Orx rats and the SO rats were given the same volume of sterile olive oil to serve as controls. For histomorphometrical analysis of the trabecular bone microarchitecture an imagej public domain image processing programme was used. Thyroid sections were analysed histologically and stereologically after visualization of follicular and C‐cells by immunohistochemical staining for thyroglobulin and CT. Thyroid follicular epithelium, interstitium, colloid and CT‐immunopositive C‐cells were examined morphometrically. Serum concentrations of osteocalcin (OC), triiodothyronine (T(3)), thyroxine (T(4)) and CT were determined as well as urinary calcium (Ca(2+)) concentrations. Genistein treatment significantly increased cancellous bone area (B.Ar), trabecular thickness (TbTh) and trabecular number (TbN) (P

Glucocorticoids affect the growth and maturation of fetal organ systems, but overexposure to exogenous glucocorticoids retard fetal growth and may alter developmental process in sensitive tissues. On the other hand, fetal ovary is not characterized by definitive follicular structure, but the clusters of germinative cells are predominant. Germ cells may be in meiotic prophase or with sign of degeneration. The aim of this study was to determine whether prenatal exposure to dexamethasone (Dx) altered normal structure and development of ovary in 19 day old rat fetuses. Pregnant females in the experimental group received subcutaneous injections of 1.0, 0.5 and 0.5 mg Dx /kg body weight on days 16–18 of pregnancy. Control mothers were injected with the same amount of saline. On day 19 of pregnancy, the dams and their fetuses were sacrificed under ether anesthesia and the fetuses were referred to as 19-day-old fetuses. Fetal ovaries were prepared for further stereological examination. The volume of the fetal ovary estimated using Cavalieri’s principle was significantly reduced after exposure to Dx by 22% (P

This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia Grant No. 173009; This study aimed to investigate effects of citrus flavanones naringenin (NAR) and hesperetin (HES) on liver antioxidant status and membrane phospholipid composition in 24-month-old rats. NAR and HES (15 mg/kg) were administrated orally to male Wistar rats, once per day, for 4 weeks. Control group received either vehicle (sunflower oil) or remained intact. The results showed decreased (p < 0.05) activity of antioxidant enzymes (AOE), specifically catalase (CAT), superoxide dismutase (SOD) 1 and glutathione reductase (GR) in the liver of intact control old-aged rats in comparison to young intact controls. Flavanone administration to old-aged males increased (p < 0.05) examined AOE activities in comparison to vehicle-administered animals. Namely, NAR was more potent in comparison to HES regarding the increase (p < 0.05) in activities of examined antioxidant enzymes (SOD 1 and 2, glutathione peroxidase-GPx and GR) and the liver glutathione (GSH), while HES elevated (p < 0.05) only activity of CAT and GR. Both flavanones significantly decreased (p < 0.05) TBARS and improved (p < 0.05) membrane phospholipid composition in favor of n-3 PUFA and n-6/n-3 PUFA ratio. Both flavanones did not affect liver histology and reduced (p < 0.05) alanine aminotransferase and aspartate aminotransferase levels in serum. The results of this study indicate beneficial potential of citrus flavanones in the old-aged rat liver

The culminating phase of ageing in males-andropause is characterized by enhanced activity of the hypothalamic-pituitary-adrenal axis and frequent glucocorticoid excess. In parallel, free testosterone deficiency provides the baseline hormonal milieu for the ageing male. The aim of this study was to illustrate (using diverse microscopic and biochemical methodologies) the effects of testosterone application on the capacity for adrenocorticotropic hormone (ACTH) and corticosterone secretion in a rat model of the andropause. Middle-aged Wistar rats were divided into sham-operated (SO; n = 8), orchidectomized (Orx; n = 8) and testosterone treated orchidectomized (Orx +T; n = 8) groups. Testosterone propionate (5 mg/kg b.w./day) was administered for three weeks, while SO and Orx groups received the vehicle alone. ACTH cells and the adrenal cortex were stained using immuno-histochemical, immuno-fluorescent and histochemical procedures. Circulating concentrations of testosterone, estradiol, ACTH and corticosterone, as well as the adrenal tissue corticosterone levels were measured by immunoassays. Testosterone application led to increased (p < 0.05) serum concentrations of sex steroids. Consequently, in Orx+T rats the ACTH cell nuclei volume increased (p < 0.05) by 34\%, while the volume density of ACTH cells and their relative intensity of fluorescence decreased (p < 0.05) by 46\% and 21\%, respectively, in comparison with the corresponding parameters in the Orx group. Testosterone also induced vasodilatation in the adrenocortical zona fasciculata, and decreased (p < 0.05) the ACTH concentrations and adrenal tissue corticosterone levels by 38\% and 31\%, respectively, compared to the Orx group. In conclusion, testosterone administration caused a decrease in the capacity for ACTH and corticosterone secretion in a rat model of the andropause. (C) 2015 Elsevier GmbH. All rights reserved. Ministry of Science, Education and Technological Development of the Republic of Serbia {[}173009]

This work was supported by the Ministry of Science, Education and Technological Development of the Republic of Serbia, Grant number 173009. We wish to express our gratitude to Ivan Spasojevic PhD, Life Systems Department, Institute for Multidisciplinary Research, Belgrade, Serbia for the valuable methodological and intellectual assistance during the experiments and manuscript preparation; Purpose: Deformability/rheologic behavior of erythrocytes are related to near-surface membrane fluidity. Specific agents can increase erythrocyte membrane fluidity in order to adjust hemodynamics in cardiovascular diseases. Grapefruit flavanone naringenin has been proposed for potential use in an alternative therapy of cardiovascular conditions. In respect to this, we assessed here effects of two nutritionally relevant concentrations of naringenin (0.1 and 1 mu g/ml) on near-surface membrane fluidity in human erythrocytes. Methods: We used electron paramagnetic resonance spectroscopy and fatty acid spin probes (5-DS and 7-DS), the spectra of which are dependent on membrane fluidity. Results: The results showed a significant (p = 0.029) increase of membrane fluidity near the hydrophilic surface in erythrocytes treated with higher concentration of naringenin. In the deeper layer, just below the erythrocyte membrane phospholipid heads, both lower and higher concentration of naringenin significantly increased membrane fluidity (p = 0.036 and p = 0.028, respectively). Conclusions: These data document the positive and dose dependent effect of naringenin on near-surface membrane fluidity in human erythrocytes, recommending its use in the cardiovascular conditions characterized by disturbed hemodynamics

The role of membrane fluidity in determining red blood cell (RBC) deformability has been suggested by a number of studies. The present investigation evaluated alterations of RBC membrane fluidity, deformability and stability in the presence of four linear alcohols (methanol, ethanol, propanol and butanol) using ektacytometry and electron paramagnetic resonance (EPR) spectroscopy. All alcohols had a biphasic effect on deformability such that it increased then decreased with increasing concentration; the critical concentration for reversal was an inverse function of molecular size. EPR results showed biphasic changes of near-surface fluidity (i.e., increase then decrease) and a decreased fluidity of the lipid core; rank order of effectiveness was butanol > propanol > ethanol > methanol, with a significant correlation between near-surface fluidity and deformability (r = 0.697; p, Turkish Academy of Sciences, NIH; Ministry of Science, Education and Technological Development of the Republic of Serbia

Soy isoflavones represent hopeful unconventional remedies in the therapy of prostate cancer. The aim of our study was to determine the effects of genistein and daidzein on the parameters that reflect metastatic potential, membrane fluidity, invasiveness and dynamic phenotype in Matrigel of LNCaP and PC-3 prostate cancer cells. Cell viability tests, using a wide range of concentrations of soy isoflavones (6-75 mu g/ml for 72 h), were conducted to determine their IC50 concentrations. Electron paramagnetic resonance investigations of prostate cancer cell membrane fluidity were performed at IC50 concentrations of genistein and daidzein (12.5 and 25 mu g/ml, respectively, for 10 min). Genistein provoked significant increases in the membrane order parameter (which is reciprocally proportional to membrane fluidity) of 0.722 +/- A 0.006 (LNCaP), 0.753 +/- A 0.010 (LNCaP + genistein), 0.723 +/- A 0.007 (PC-3) and 0.741 +/- A 0.004 (PC-3 + genistein); however, no such effects were observed for daidzein. While both genistein and daidzein reduced the proliferation of prostate cancer cells at their respective IC50 concentrations, during the 72 h of incubation only genistein provoked effects on the dynamic phenotype and decreased invasiveness. The effect was more evident in PC-3 cells compared to LNCaP cells. Our results imply that (1) invasive activity is at least partially dependent on membrane fluidity, (2) genistein may exert its antimetastatic effects by changing the mechanical properties of prostate cancer cells and (3) daidzein should be applied at higher concentrations than genistein in order to achieve pharmacological effects. Ministry of Science, Education and Technological Development of the Republic of Serbia [173009, 173013, 173014]

Endogenous androgens are involved in regulation of thyroid function and metabolism of thyroid hormones. As serum testosterone level progressively declines with age, this regulation may change. We tested how androgen deprivation, achieved by orchidectomy, affects thyroid homeostasis in middle-aged rats. Fifteen-month-old Wistar rats were orchidectomized (Orx) or sham-operated under ketamine anesthesia (15 mg/kg body weight). Five weeks after the surgery, animals were decapitated. Thyroids were used for histomorphometric and ultrastructural examinations and together with livers and pituitaries for real-time quantitative PCR and deiodinase (DIO) activity measurements. Serum testosterone, TSH, l-thyroxine (T4), and cholesterol (Chol) levels were determined. As expected, middle-aged control rats had lower (P4 compared with 3-month-old males. In the Orx middle-aged group, we detected diminished serum testosterone (P4 levels, and higher Chol level (PPDio1 gene expression and DIO1 activity were decreased (PTSHβ, Dio1, and Dio2 mRNAs did not change, while DIO2 activity decreased (P4 and TSH. However, decreased liver DIO1 and pituitary DIO2 enzyme activities indicate compensatory–adaptive changes in local T3 production.