TY  - CONF
AU  - Šošić-Jurjević, Branka
AU  - Janković, Snežana
AU  - Lutjohann, Dieter
AU  - Jarić, Ivana
AU  - Miler, Marko
AU  - Filipović, Branko
AU  - Ajdžanović, Vladimir
AU  - Milošević, Verica
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6362
AB  - Hypercholesterolemia is associated with athero-thrombotic disease, a leading cause of mortality worldwide. Advances in both dietary and pharmacological interventions contribute to prevention and treatment of modifiable risk factors.Purified soybean phytoestrogens, isoflavones genistein (GEN) and daidzein (DAI), were reported to exert moderate cholesterol-lowering effect. In this research first we studied age-related modifications in hepatic cholesterol metabolism and serum estradiol concentration of acyclic middle-aged (MA) female rats. Then we tested if purified isoflavones may prevent or reverse these changes. Serum and hepatic total cholesterol (TCH), bile acid and cholesterol precursors were determined by comparing data obtained for MA with young adult (YA) intact (IC) females. Effects of subcutaneously administered GEN or DAI (35 mg/kg per daily during four weeks) to MA rats were evaluated vs vehicle (sterile olive oil) – treated MA females. After decapitation, perfused rat livers and serum were used to determine total cholesterol (TCH), its oxidative metabolites (7α-, 27- and 24-hydroxycholesterol) and precursors (lanosterol, desmosterol, dihydro-lano sterol and lathosterol), using gas chromatography/mass spectrometry. Serum estradiol was determined by ECLIA. MA IC females were characterized by: higher (P<0.05) serum TCH, lower (P<0.05) hepatic TCH and its biosynthetic precursors, lower (P<0.05) hepatic7α-hydroxycholesterol but elevated (P<0.05) 27- and 24- hydroxycholesterol in comparison to YA IC. Both GEN and DAI decreased (P<0.05) hepatic 27-hydroxycholesterol, with no effect on any other parameter of cholesterol metabolism. We obtained age-related reduction of serum estradiol, which was reversed by both soybean phytoestrogens. In conclusion, age-related dyslipidemia was associated with reduced 7α-hydroxycholesterol, main intermediate of neutral pathway, and higher 27—hydroxycholesterol, main intermediate of alternative acidic pathway of Chol degradation to bile acid. Both GEN and DAI lowered hepatic 27- hydroxycholesterol, which might be associated with elevated serum estradiol concentrations. Further research is needed to examine this possibility.
PB  - Bioscientifica
C3  - 19th European Congress of Endocrinology; 2017 May 20-23; Lisbon, Portugal. (Endocrine Abstracts; Vol. 49).
T1  - Soybean phytoestrogens reduce 27-hydroxycholesterol concentration in the liver of middle-aged female rats
DO  - 10.1530/endoabs.49.EP359
DO  - 1470-3947
SP  - EP359
ER  - 

@conference{
author = "Šošić-Jurjević, Branka and Janković, Snežana and Lutjohann, Dieter and Jarić, Ivana and Miler, Marko and Filipović, Branko and Ajdžanović, Vladimir and Milošević, Verica",
year = "2017",
abstract = "Hypercholesterolemia is associated with athero-thrombotic disease, a leading cause of mortality worldwide. Advances in both dietary and pharmacological interventions contribute to prevention and treatment of modifiable risk factors.Purified soybean phytoestrogens, isoflavones genistein (GEN) and daidzein (DAI), were reported to exert moderate cholesterol-lowering effect. In this research first we studied age-related modifications in hepatic cholesterol metabolism and serum estradiol concentration of acyclic middle-aged (MA) female rats. Then we tested if purified isoflavones may prevent or reverse these changes. Serum and hepatic total cholesterol (TCH), bile acid and cholesterol precursors were determined by comparing data obtained for MA with young adult (YA) intact (IC) females. Effects of subcutaneously administered GEN or DAI (35 mg/kg per daily during four weeks) to MA rats were evaluated vs vehicle (sterile olive oil) – treated MA females. After decapitation, perfused rat livers and serum were used to determine total cholesterol (TCH), its oxidative metabolites (7α-, 27- and 24-hydroxycholesterol) and precursors (lanosterol, desmosterol, dihydro-lano sterol and lathosterol), using gas chromatography/mass spectrometry. Serum estradiol was determined by ECLIA. MA IC females were characterized by: higher (P<0.05) serum TCH, lower (P<0.05) hepatic TCH and its biosynthetic precursors, lower (P<0.05) hepatic7α-hydroxycholesterol but elevated (P<0.05) 27- and 24- hydroxycholesterol in comparison to YA IC. Both GEN and DAI decreased (P<0.05) hepatic 27-hydroxycholesterol, with no effect on any other parameter of cholesterol metabolism. We obtained age-related reduction of serum estradiol, which was reversed by both soybean phytoestrogens. In conclusion, age-related dyslipidemia was associated with reduced 7α-hydroxycholesterol, main intermediate of neutral pathway, and higher 27—hydroxycholesterol, main intermediate of alternative acidic pathway of Chol degradation to bile acid. Both GEN and DAI lowered hepatic 27- hydroxycholesterol, which might be associated with elevated serum estradiol concentrations. Further research is needed to examine this possibility.",
publisher = "Bioscientifica",
journal = "19th European Congress of Endocrinology; 2017 May 20-23; Lisbon, Portugal. (Endocrine Abstracts; Vol. 49).",
title = "Soybean phytoestrogens reduce 27-hydroxycholesterol concentration in the liver of middle-aged female rats",
doi = "10.1530/endoabs.49.EP359, 1470-3947",
pages = "EP359"
}

Šošić-Jurjević, B., Janković, S., Lutjohann, D., Jarić, I., Miler, M., Filipović, B., Ajdžanović, V.,& Milošević, V.. (2017). Soybean phytoestrogens reduce 27-hydroxycholesterol concentration in the liver of middle-aged female rats. in 19th European Congress of Endocrinology; 2017 May 20-23; Lisbon, Portugal. (Endocrine Abstracts; Vol. 49).
Bioscientifica., EP359.
https://doi.org/10.1530/endoabs.49.EP359

Šošić-Jurjević B, Janković S, Lutjohann D, Jarić I, Miler M, Filipović B, Ajdžanović V, Milošević V. Soybean phytoestrogens reduce 27-hydroxycholesterol concentration in the liver of middle-aged female rats. in 19th European Congress of Endocrinology; 2017 May 20-23; Lisbon, Portugal. (Endocrine Abstracts; Vol. 49).. 2017;:EP359.
doi:10.1530/endoabs.49.EP359 .

Šošić-Jurjević, Branka, Janković, Snežana, Lutjohann, Dieter, Jarić, Ivana, Miler, Marko, Filipović, Branko, Ajdžanović, Vladimir, Milošević, Verica, "Soybean phytoestrogens reduce 27-hydroxycholesterol concentration in the liver of middle-aged female rats" in 19th European Congress of Endocrinology; 2017 May 20-23; Lisbon, Portugal. (Endocrine Abstracts; Vol. 49). (2017):EP359,
https://doi.org/10.1530/endoabs.49.EP359 . .

TY  - JOUR
AU  - Šošić-Jurjević, Branka
AU  - Lütjohann, Dieter
AU  - Jarić, Ivana
AU  - Miler, Marko
AU  - Vojnović-Milutinović, Danijela
AU  - Filipović, Branko
AU  - Ajdžanović, Vladimir
AU  - Renko, Kostja
AU  - Wirth, Eva Katrin
AU  - Janković, Snežana
AU  - Kӧhrle, Josef
AU  - Milošević, Verica
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S053155651630585X
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2722
AB  - Soy-food and its isoflavones, genistein (G) and daidzein (D), were reported to exert mild cholesterol-lowering effect, but the underlying mechanism is still unclear. In this research, first we studied age-related alterations in hepatic cholesterol metabolism of acyclic middle-aged (MA) female rats. Then we tested if purified isoflavones may prevent or reverse these changes, and whether putative changes in hepatic thyroid hormone availability may be associated with this effect. Serum and hepatic total cholesterol (TChol), bile acid and cholesterol precursors, as well as serum TSH and T4 concentrations, hepatic deiodinase (Dio) 1 enzyme activity and MCT8 protein expression were determined by comparing data obtained for MA with young adult (YA) intact (IC) females. Effects of subcutaneously administered G or D (35 mg/kg) to MA rats were evaluated versus vehicle-treated MA females. MA IC females were characterized by: higher (p < 0.05) serum TChol, lower (p < 0.05) hepatic TChol and its biosynthetic precursors, lower (p < 0.05) hepatic 7α-hydroxycholesterol but elevated (p < 0.05) 27- and 24-hydroxycholesterol in comparison to YA IC. Both isoflavone treatments decreased (p < 0.05) hepatic 27-hydroxycholesterol, G being more effective than D, without affecting any other parameter of Chol metabolism. Only G elevated hepatic Dio1 activity (p < 0.05). In conclusion, age-related hypercholesteremia was associated with lower hepatic Chol synthesis and shift from main neutral (lower 7α-hydroxycholesterol) to alternative acidic pathway (higher 27-hydroxycholesterol) of Chol degradation to bile acid. Both isoflavones lowered hepatic 27-hydroxycholesterol, which may be considered beneficial. Only G treatment increased hepatic Dio1 activity, thus indicating local increase in thyroid hormones, obviously insufficient to induce prominent cholesterol-lowering effect.
T2  - Experimental Gerontology
T1  - Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats
VL  - 92
DO  - 10.1016/j.exger.2017.03.016
SP  - 74
EP  - 81
ER  - 

@article{
author = "Šošić-Jurjević, Branka and Lütjohann, Dieter and Jarić, Ivana and Miler, Marko and Vojnović-Milutinović, Danijela and Filipović, Branko and Ajdžanović, Vladimir and Renko, Kostja and Wirth, Eva Katrin and Janković, Snežana and Kӧhrle, Josef and Milošević, Verica",
year = "2017",
abstract = "Soy-food and its isoflavones, genistein (G) and daidzein (D), were reported to exert mild cholesterol-lowering effect, but the underlying mechanism is still unclear. In this research, first we studied age-related alterations in hepatic cholesterol metabolism of acyclic middle-aged (MA) female rats. Then we tested if purified isoflavones may prevent or reverse these changes, and whether putative changes in hepatic thyroid hormone availability may be associated with this effect. Serum and hepatic total cholesterol (TChol), bile acid and cholesterol precursors, as well as serum TSH and T4 concentrations, hepatic deiodinase (Dio) 1 enzyme activity and MCT8 protein expression were determined by comparing data obtained for MA with young adult (YA) intact (IC) females. Effects of subcutaneously administered G or D (35 mg/kg) to MA rats were evaluated versus vehicle-treated MA females. MA IC females were characterized by: higher (p < 0.05) serum TChol, lower (p < 0.05) hepatic TChol and its biosynthetic precursors, lower (p < 0.05) hepatic 7α-hydroxycholesterol but elevated (p < 0.05) 27- and 24-hydroxycholesterol in comparison to YA IC. Both isoflavone treatments decreased (p < 0.05) hepatic 27-hydroxycholesterol, G being more effective than D, without affecting any other parameter of Chol metabolism. Only G elevated hepatic Dio1 activity (p < 0.05). In conclusion, age-related hypercholesteremia was associated with lower hepatic Chol synthesis and shift from main neutral (lower 7α-hydroxycholesterol) to alternative acidic pathway (higher 27-hydroxycholesterol) of Chol degradation to bile acid. Both isoflavones lowered hepatic 27-hydroxycholesterol, which may be considered beneficial. Only G treatment increased hepatic Dio1 activity, thus indicating local increase in thyroid hormones, obviously insufficient to induce prominent cholesterol-lowering effect.",
journal = "Experimental Gerontology",
title = "Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats",
volume = "92",
doi = "10.1016/j.exger.2017.03.016",
pages = "74-81"
}

Šošić-Jurjević, B., Lütjohann, D., Jarić, I., Miler, M., Vojnović-Milutinović, D., Filipović, B., Ajdžanović, V., Renko, K., Wirth, E. K., Janković, S., Kӧhrle, J.,& Milošević, V.. (2017). Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats. in Experimental Gerontology, 92, 74-81.
https://doi.org/10.1016/j.exger.2017.03.016

Šošić-Jurjević B, Lütjohann D, Jarić I, Miler M, Vojnović-Milutinović D, Filipović B, Ajdžanović V, Renko K, Wirth EK, Janković S, Kӧhrle J, Milošević V. Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats. in Experimental Gerontology. 2017;92:74-81.
doi:10.1016/j.exger.2017.03.016 .

Šošić-Jurjević, Branka, Lütjohann, Dieter, Jarić, Ivana, Miler, Marko, Vojnović-Milutinović, Danijela, Filipović, Branko, Ajdžanović, Vladimir, Renko, Kostja, Wirth, Eva Katrin, Janković, Snežana, Kӧhrle, Josef, Milošević, Verica, "Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats" in Experimental Gerontology, 92 (2017):74-81,
https://doi.org/10.1016/j.exger.2017.03.016 . .

TY  - JOUR
AU  - Šošić-Jurjević, Branka
AU  - Filipović, Branko
AU  - Wirth, Eva Katrin
AU  - Živanović, Jasmina
AU  - Radulović, Niko
AU  - Janković, Snežana
AU  - Milošević, Verica
AU  - Köhrle, Josef
PY  - 2014
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6134
AB  - We previously reported that genistein (G) and daidzein (D) administered subcutaneously (10 mg/kg) induce changes in the angio-follicular units of the thyroid gland, reduce concentration of total thyroid hormones (TH) and increase thyrotropin (TSH) in serum of orchidectomized middle-aged (16-month-old) rats. To further investigate these effects, we now examined expression levels of the thyroglobulin (Tg), thyroperoxidase (Tpo), vascular endothelial growth factor A (Vegfa) and deiodinase type 1 (Dio 1) genes in the thyroid; in the pituitary, genes involved in TH feedback control (Tsh beta, Dio 1, Dio 2, Trh receptor); and in the liver and kidney, expression of T-3-activated genes Dio 1 and Spot 14, as well as transthyretin (Ttr), by quantitative real-time PCR. We also analyzed TPO-immunopositivity and immunofluorescence of T-4 bound to Tg, determined thyroid T-4 levels and measured deiodinase enzyme activities in examined organs. Decreased expression of Tg and Tpo genes (p < 0.05) correlated with immunohistochemical staining results, and together with decreased serum total T-4 levels, indicates decreased Tg and TH synthesis following treatments with both isoflavones. However, expression of Spot 14 (p < 0.05) gene in liver and kidney was up-regulated, and liver Dio 1 expression and activity (p < 0.05) increased. At the level of pituitary, no significant change in gene expression levels, or Dio 1 and 2 enzyme activities was observed. In conclusion, both G and D impaired Tg and TH synthesis, but at the same time increased tissue availability of TH in peripheral tissues of Orx middle-aged rats.
PB  - Elsevier Inc
T2  - Toxicology and Applied Pharmacology
T1  - Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats
IS  - 2
VL  - 278
DO  - 10.1016/j.taap.2014.04.018
SP  - 124
EP  - 134
ER  - 

@article{
author = "Šošić-Jurjević, Branka and Filipović, Branko and Wirth, Eva Katrin and Živanović, Jasmina and Radulović, Niko and Janković, Snežana and Milošević, Verica and Köhrle, Josef",
year = "2014",
abstract = "We previously reported that genistein (G) and daidzein (D) administered subcutaneously (10 mg/kg) induce changes in the angio-follicular units of the thyroid gland, reduce concentration of total thyroid hormones (TH) and increase thyrotropin (TSH) in serum of orchidectomized middle-aged (16-month-old) rats. To further investigate these effects, we now examined expression levels of the thyroglobulin (Tg), thyroperoxidase (Tpo), vascular endothelial growth factor A (Vegfa) and deiodinase type 1 (Dio 1) genes in the thyroid; in the pituitary, genes involved in TH feedback control (Tsh beta, Dio 1, Dio 2, Trh receptor); and in the liver and kidney, expression of T-3-activated genes Dio 1 and Spot 14, as well as transthyretin (Ttr), by quantitative real-time PCR. We also analyzed TPO-immunopositivity and immunofluorescence of T-4 bound to Tg, determined thyroid T-4 levels and measured deiodinase enzyme activities in examined organs. Decreased expression of Tg and Tpo genes (p < 0.05) correlated with immunohistochemical staining results, and together with decreased serum total T-4 levels, indicates decreased Tg and TH synthesis following treatments with both isoflavones. However, expression of Spot 14 (p < 0.05) gene in liver and kidney was up-regulated, and liver Dio 1 expression and activity (p < 0.05) increased. At the level of pituitary, no significant change in gene expression levels, or Dio 1 and 2 enzyme activities was observed. In conclusion, both G and D impaired Tg and TH synthesis, but at the same time increased tissue availability of TH in peripheral tissues of Orx middle-aged rats.",
publisher = "Elsevier Inc",
journal = "Toxicology and Applied Pharmacology",
title = "Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats",
number = "2",
volume = "278",
doi = "10.1016/j.taap.2014.04.018",
pages = "124-134"
}

Šošić-Jurjević, B., Filipović, B., Wirth, E. K., Živanović, J., Radulović, N., Janković, S., Milošević, V.,& Köhrle, J.. (2014). Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats. in Toxicology and Applied Pharmacology
Elsevier Inc., 278(2), 124-134.
https://doi.org/10.1016/j.taap.2014.04.018

Šošić-Jurjević B, Filipović B, Wirth EK, Živanović J, Radulović N, Janković S, Milošević V, Köhrle J. Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats. in Toxicology and Applied Pharmacology. 2014;278(2):124-134.
doi:10.1016/j.taap.2014.04.018 .

Šošić-Jurjević, Branka, Filipović, Branko, Wirth, Eva Katrin, Živanović, Jasmina, Radulović, Niko, Janković, Snežana, Milošević, Verica, Köhrle, Josef, "Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats" in Toxicology and Applied Pharmacology, 278, no. 2 (2014):124-134,
https://doi.org/10.1016/j.taap.2014.04.018 . .