Regenerative role of Genistein treatment on Fibrotic and inflammatory Biomarkers Alteration in the Lung of Estrogen deficient Rats

Abstract Background Phytoestrogens are suggested to have estrogenic effects in the pulmonary system and have been revealed with a few adverse side effects. In this study, we tried to investigate the effect of genistein treatment on estrogen deficiency-induced lung injury and demonstrating whether genistein supplementation could replace estrogen hormone in postmenopausal women. Methods Forty adult female rats were divided into four groups; sham: rats that underwent surgery without ovariectomy, OVX: rats that underwent ovariectomies, OVX.E: ovariectomized rats with eight weeks period of estrogen treatment (20µg/kg/day), OVX.Gen: ovariectomized rats with eight week period of genistein treatment (1mg/kg/day). At the end of the experiment, lung tissue was removed and inflammatory and fibrotic biomarkers were evaluated with western blotting technique. Hematoxylin-eosin and immunohistochemical staining were used to evaluate histomorphological changes in the lung tissue. Results Genistein treatment restored ERK1/2, TGFβ1, MMP2, and IL1β, Bcl-2, and caspase3 expression levels, implying the effectiveness of genistein supplementation in targeting estrogen deficiency symptoms. Conclusions Genistein supplementation exerted protective effects against ovariectomy-induced lung injury with reducing inflammation and fibrosis, moreover, it can be recommended as a natural alternative to postmenopausal hormone therapy.

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Prenylated Isoflavonoids-Rich Extract of Erythrinae Cortex Exerted Bone Protective Effects by Modulating Gut Microbial Compositions and Metabolites in Ovariectomized Rats

Nutrients ◽

10.3390/nu13092943 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2943

Author(s):

Hui-Hui Xiao ◽

Xueli Yu ◽

Chen Yang ◽

Chi-On Chan ◽

Lu Lu ◽

...

Keyword(s):

Bone Microarchitecture ◽

Cathepsin K ◽

Short Chain Fatty Acids ◽

Female Rats ◽

Ovariectomized Rats ◽

Protective Effects ◽

Sprague Dawley ◽

Mineral Density ◽

Beneficial Effects ◽

Ovx Rats

Flavonoids, found in a wide variety of foods and plants, are considered to play an important role in the prevention and treatment of osteoporosis. Our previous studies demonstrated that Erythrina cortex extract (EC) rich in prenylated isoflavonoids exerted bone protective effects in ovariectomized (OVX) rats. The present study aimed to investigate the interactions of gut microbiota with the EC extract to explore the underlying mechanisms involved in its beneficial effects on bone. Sprague-Dawley female rats of 3-months-old were ovariectomized and treated with EC extract for 12 weeks. EC extract reversed ovariectomy-induced deterioration of bone mineral density and bone microarchitecture as well as downregulated cathepsin K (Ctsk) and upregulated runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) in the tibia of OVX rats. Its protective effects on bone were correlated with changes in microbial richness and the restorations of several genera. EC increased the serum circulating levels of acetate and propionate in OVX rats. We conclude that the bone protective effects of EC extract were associated with the changes in microbial compositions and serum short chain fatty acids (SCFAs) in OVX rats.

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Genistein acts in bone metabolism and improves peri-implant healing in rats with estrogen deficiency

Research Society and Development ◽

10.33448/rsd-v10i5.15061 ◽

2021 ◽

Vol 10 (5) ◽

pp. e36410515061

Author(s):

Naara Gabriela Monteiro ◽

Fábio Roberto De Souza Batista ◽

Maria Isabela Lopes Gandolfo ◽

Leonardo Perez Faverani ◽

Letícia Pitol Palin ◽

...

Keyword(s):

Bone Healing ◽

Saline Solution ◽

Bone Volume ◽

Female Rats ◽

Ovariectomized Rats ◽

Significance Level ◽

Osteoblastic Activity ◽

Bilateral Ovariectomy ◽

Ovx Rats ◽

Genistein Treatment

The present study aimed to evaluate the peri-implantar bone healing in the presence of genistein treatment in ovariectomized rats. Thirty female rats with 4 months old were divided into 3 groups according to the experimental condition and the drug treatment: SHAM (rats submitted to the fictional surgery and gavage with 0.9% saline solution); OVX (rats submitted to bilateral ovariectomy and gavage with 0.9% saline solution); OVX GEN (rats submitted to bilateral ovariectomy and gavage with 1mg/day of genistein). 60 implants were installed, with two implants in each animal. The calcified group was subjected microcomputerized tomography and the parameters analysed was bone volume per tissue volume (BV/TV) and connective density (Cnn.Dn). The decalcified samples were evaluated through immunolabeling analysis, in order to detect the presence of RUNX2, Alkaline Phosphatase, Osteocalcin, Osteopontin and TRAP. All the quantitative data were submitted to the normality curve to determine the most adequate test. The significance level of p<0.05 was considered for all tests. The morphometric analysis of the OVX GEN group showed higher percentage of bone volume and lower connective density when compared with OVX. Immunohistochemical analysis favors expression. For the markers that positively label osteoblastic activity. This study shows that genistein therapy improves peri-implant bone healing in ovariectomized rats.

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Negligible Effect of Estrogen Deficiency on Development of Skeletal Changes Induced by Type 1 Diabetes in Experimental Rat Models

Mediators of Inflammation ◽

10.1155/2020/2793804 ◽

2020 ◽

Vol 2020 ◽

pp. 1-21

Author(s):

Aleksandra Janas ◽

Ewa Kruczek ◽

Piotr Londzin ◽

Sławomir Borymski ◽

Zenon P. Czuba ◽

...

Keyword(s):

Mechanical Properties ◽

Bone Resorption ◽

Bone Mass ◽

Cancellous Bone ◽

Maximum Load ◽

Estrogen Deficiency ◽

Female Rats ◽

Skeletal System ◽

Tibial Metaphysis ◽

Ovx Rats

Although postmenopausal osteoporosis often occurs concurrently with diabetes, little is known about interactions between estrogen deficiency and hyperglycemia in the skeletal system. In the present study, the effects of estrogen deficiency on the development of biochemical, microstructural, and mechanical changes induced by streptozotocin-induced diabetes mellitus (DM) in the rat skeletal system were investigated. The experiments were carried out on nonovariectomized (NOVX) and ovariectomized (OVX) control and diabetic mature female Wistar rats. Serum levels of bone turnover markers (CTX-I and osteocalcin) and 23 cytokines, bone mass and mineralization, histomorphometric parameters, and mechanical properties of cancellous and compact bone were determined. The results were subjected to two-way ANOVA and principal component analysis (PCA). Estrogen deficiency induced osteoporotic changes, with increased bone resorption and formation, and worsening of microstructure (femoral metaphyseal BV/TV decreased by 13.0%) and mechanical properties of cancellous bone (the maximum load in the proximal tibial metaphysis decreased by 34.2%). DM in both the NOVX and OVX rats decreased bone mass, increased bone resorption and decreased bone formation, and worsened cancellous bone microarchitecture (for example, the femoral metaphyseal BV/TV decreased by 17.3% and 18.1%, respectively, in relation to the NOVX controls) and strength (the maximum load in the proximal tibial metaphysis decreased by 35.4% and 48.1%, respectively, in relation to the NOVX controls). Only in the diabetic rats, profound increases in some cytokine levels were noted. In conclusion, the changes induced by DM in female rats were only slightly intensified by estrogen deficiency. Despite similar effects on bone microstructure and strength, the influence of DM on the skeletal system was based on more profound systemic homeostasis changes than those induced by estrogen deficiency.

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Modulating Effects of Cholecalciferol Treatment on Estrogen Deficiency-Induced Anxiety-Like Behavior of Adult Female Rats

Folia Medica ◽

10.1515/folmed-2017-0022 ◽

2017 ◽

Vol 59 (2) ◽

pp. 139-158 ◽

Cited By ~ 5

Author(s):

Julia Fedotova ◽

Daria Zarembo ◽

Jozef Dragasek ◽

Martin Caprnda ◽

Peter Kruzliak ◽

...

Keyword(s):

Elevated Plus Maze ◽

Open Field Test ◽

Estrogen Deficiency ◽

Female Rats ◽

Ovx Rats ◽

Plus Maze ◽

17Β Estradiol ◽

Experimental Rat Model ◽

High Doses ◽

Estradiol 17Β

AbstractBackground:Vitamin D can be one of the candidate substances that are used as additional supplementation in the treatment of anxiety-related disorders in women with estrogen imbalance.Materials and methods:The aim of the present study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg/day, s.c.) on the anxiety-like behavior and monoamines levels in the rat hippocampus following ovariectomy in female rats. Cholecalciferol was given to ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E2, 0.5 μg/rat, s.c.). The anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light-dark tests (LDT), locomotor and grooming activities were assessed in the open-field test (OFT).Results:Cholecalciferol in high doses alone or in combination with 17β-E2-induced anxiolytic-like effects in OVX and OVX rats treated with 17β-E2as evidenced in the EPM and LDT tests, and increased grooming activity in the OFT test. We found that DA and 5-HT levels increased while 5-HT turnover in the hippocampus decreased in these groups of OVX rats.Conclusion:Our results indicate that cholecalciferol in high doses has a marked anxiolytic-like effect due to an increase in the monoamines levels in the experimental rat model of estrogen deficiency.

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Short- and long-term effects of calcium and exercise on bone mineral density in ovariectomized rats

British Journal Of Nutrition ◽

10.1079/bjn2001428 ◽

2001 ◽

Vol 86 (4) ◽

pp. 521-527 ◽

Cited By ~ 18

Author(s):

Joseé Gala ◽

Manuel Di´az-curiel ◽

Concepcioó de la Piedra ◽

Jesu´s Calero

Keyword(s):

Bone Mineral Density ◽

Bone Loss ◽

Bone Mineral ◽

Exercise Programme ◽

Female Rats ◽

Ovariectomized Rats ◽

Standard Diet ◽

Mineral Density ◽

Left Femur ◽

Ovx Rats

At the level of prevention of bone mineral loss produced by ovariectomy, the aim of the present study was to determine the effect produced by supplementation of Ca in the diet and a moderate exercise programme (treadmill), simultaneously or separately, in ovariectomized rats, an experimental model of postmenopausal bone loss. Female Wistar rats (n110, 15 weeks old) were divided into five groups: (1) OVX, rats ovariectomized at 15 weeks of age, fed a standard diet; (2) SHAM, rats sham operated at 15 weeks of age, fed a standard diet; (3) OVX–EX, ovariectomized rats, fed a standard diet and performing the established exercise programme; (4) OVX–Ca, ovariectomized rats fed a diet supplemented with Ca; (5) OVX–EXCa, ovariectomized rats with the exercise programme and diet supplemented with Ca. The different treatments were initiated 1 week after ovariectomy and were continued for 13 weeks for subgroup 1 and 28 weeks for subgroup 2, to look at the interaction of age and time passed from ovariectomy on the treatments. Bone mineral density (BMD) was determined, at the end of the study, in the lumbar spine (L2, L3 and L4) and in the left femur using a densitometer. Bone turnover was also estimated at the end of the study, measuring the serum formation marker total alkaline phosphatase (AP) and the resorption marker serum tartrate-resistant acid phosphatase (TRAP). As expected, OVX rats showed a significant decrease (P<0·05) in BMD, more pronounced in subgroup 2, and a significant increase in AP and TRAP with regard to their respective SHAM group. The simultaneous treatment with Ca and exercise produced the best effects on lumbar and femoral BMD of ovariectomized rats, partially avoiding bone loss produced by ovariectomy, although it was not able to fully maintain BMD levels of intact animals. This combined treatment produced a significant increase in AP, both in subgroups 1 and 2, and a decrease in TRAP in subgroup 1, with regard to OVX group. The exercise treatment alone was able to produce an increase in BMD with regard to OVX group only in subgroup 1 of rats (younger animals and less time from ovariectomy), but not in subgroup 2. In agreement with this, there was an increase of AP in both subgroups, lower than that observed in animals submitted to exercise plus Ca supplement, and a decrease of TRAP in subgroup 1, without significant changes in this marker in the older rats. Ca treatment did not produce any significant effect on BMD in OVX rats in both subgroups of animals, showing a decrease of AP and TRAP levels in the younger animals with no significant variations in markers of bone remodelling in the older female rats compared with their respective OVX group.

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Therapeutic Effects ofCortex acanthopanacisAqueous Extract on Bone Metabolism of Ovariectomized Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/492627 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Zhiguo Zhang ◽

Jiazi Dong ◽

Meijie Liu ◽

Yan Li ◽

Jinghua Pan ◽

...

Keyword(s):

Aqueous Extract ◽

Interleukin 1 ◽

Inhibitory Effect ◽

Control Agent ◽

The Body ◽

Female Rats ◽

Ovariectomized Rats ◽

Therapeutic Effects ◽

Mineral Density ◽

Ovx Rats

The aim of this study was to evaluate effects of aqueous extract fromCortex acanthopanacis(CAE) on osteoporosis rats induced by ovariectomy (OVX) using aqueous extract fromFolium Epimedii(FEE) as positive control agent. Three-month-old female rats that underwent OVX were treated with CAE. After 12 weeks, bone mineral density (BMD) and indices of bone histomorphometry of tibia were measured. Levels of protein and mRNA expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) in tibia were evaluated. In addition, the serum concentrations of osteocalcin (OC), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), calcitonin (CT), and parathyroid hormone (PTH) were determined. Administration of CAE significantly prevented OVX-induced rats from gain of the body weight. Treatment with CAE increased bone mass remarkably and showed a significant inhibitory effect on bone resorption by downregulating significantly the expression of RANKL in tibia of OVX rats. Meanwhile, treatment of CAE significantly reduced serum level of IL-1βand increased level of CT in OVX rats. This suggests that CAE has the potential to be used as an alternative therapeutic agent for postmenopausal osteoporosis.

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Testosterone enhances estradiol's cardioprotection in ovariectomized rats

Journal of Endocrinology ◽

10.1530/joe-11-0181 ◽

2011 ◽

Vol 212 (1) ◽

pp. 61-69 ◽

Cited By ~ 14

Author(s):

Aiying Liu ◽

Liping Gao ◽

Shoulei Kang ◽

Ying Liu ◽

Chuanying Xu ◽

...

Keyword(s):

Ventricular Myocytes ◽

Contractile Function ◽

Ischemia Reperfusion ◽

Testosterone Replacement ◽

Ovariectomized Rats ◽

Sham Operation ◽

Protective Effects ◽

Sprague Dawley ◽

Ovx Rats ◽

Ldh Release

After menopause, the development of cardiovascular disease (CVD) is due not only to estrogen decline but also to androgen decline. This study examined the effects of either estradiol (E2) or testosterone replacement alone or E2–testosterone combination on isolated myocytes in ovariectomized (Ovx) rats subjected to ischemia/reperfusion (I/R). Furthermore, we determined whether the effects are associated with β2-adrenoceptor (β2-AR). Five groups of adult female Sprague–Dawley rats were used: Sham operation (Sham) rats, bilateral Ovx rats, Ovx rats with E2 40 μg/kg per day (Ovx+E), Ovx rats with testosterone 150 μg/kg per day (Ovx+T), and Ovx rats with E2 40 μg/kg per day+testosterone 150 μg/kg per day (Ovx+E/T). We determined the lactate dehydrogenase (LDH) release, percentage of rod-shaped cells and apoptosis of ventricular myocytes from rats of all groups subjected to I/R. Then, we determined the above indices and contractile function with or without a selective β2-AR antagonist ICI 118 551. We also determined the expression of β2-AR. Our data show that either E2 or testosterone replacement alone or E2 and testosterone in combination decreased the LDH release, increased the percentage of rod-shaped cells, reduced apoptotic cells (%), and combination treatment appeared to be more effective than either E2 or testosterone replacement alone. ICI 118 551 abolished the effects of the three. Combination supplementation also enhanced the expression of β2-AR. We concluded that in Ovx rats, testosterone enhances E2's cardioprotection, while E2 and testosterone in combination was more effective and the protective effects may be associated with β2-AR. The study highlights the potential therapeutic application for CVD in postmenopausal women.

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Long-Term Therapy with a New Chemically Modified Tetracycline (CMT-8) Inhibits Bone Loss in Femurs of Ovariectomized Rats

Advances in Dental Research ◽

10.1177/08959374980120012501 ◽

1998 ◽

Vol 12 (1) ◽

pp. 76-81 ◽

Cited By ~ 6

Author(s):

T. Sasaki ◽

N.S. Ramamurthy ◽

L.M. Golub

Keyword(s):

Bone Loss ◽

Bone Formation ◽

Trabecular Bone ◽

Female Rats ◽

Ovariectomized Rats ◽

Term Therapy ◽

Ovx Rats ◽

Trabecular Bone Loss ◽

Bone Trabeculae

The effect of a new non-antimicrobial analog of tetracycline (CMT-8) on bone loss in ovariectomized (OVX) rats was examined. Three-month-old female rats were ovariectomized, and one week later, were distributed into 3 groups: sham-operated non-OVX controls, vehicle-treated OVX controls, and CMT-8-treated OVX rats. After 145 days of daily CMT-8 administration, the intact femurs were dissected and examined by several histological and histomorphometric techniques. OVX significantly (p < 0.01) decreased trabecular bone volume by 53.4% in the metaphyses compared with sham-operated controls. CMT-8 therapy produced a significant (p < 0.05) inhibition of trabecular bone loss and also induced bone formation in the OVX rats. Of interest, the newly synthesized bone in the CMT-treated OVX rats was found to increase the "connectivity" of the trabecular "struts" by bridging the adjacent longitudinal bone trabeculae, forming dense, platelike bone trabeculae. These results strongly suggest that long-term CMT-8 therapy effectively inhibits bone loss after OVX, not only by inhibiting bone resorption but also by inducing new bone formation in the trabecular areas of long bones.

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High-impact exercise strengthens bone in osteopenic ovariectomized rats with the same outcome as Sham rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.00781.2002 ◽

2003 ◽

Vol 95 (3) ◽

pp. 1032-1037 ◽

Cited By ~ 49

Author(s):

Akiko Honda ◽

Naota Sogo ◽

Seigo Nagasawa ◽

Takuya Shimizu ◽

Yoshihisa Umemura

Keyword(s):

Bone Mass ◽

Female Rats ◽

Ovariectomized Rats ◽

Middle Aged ◽

Mineral Density ◽

Beneficial Effects ◽

Ovx Rats ◽

Jump Exercise ◽

Body Weights ◽

The Right

The effect of jump exercise on middle-aged osteopenic rats was investigated. Forty-two 9-mo-old female rats were either sham-operated (Sham) or ovariectomized (OVX). Three months after surgery, the rats were divided into the following groups: Sham sedentary, Sham exercised, OVX sedentary, and OVX exercised. Rats in the exercise groups jumped 10 times/day, 5 days/wk, for 8 wk, with a jumping height of 40 cm. Less than 1 min was required for the jump training. After the experiment, the right tibia and femur were dissected, and blood was obtained from each rat. OVX rats were observed to have increased body weights and decreased bone mass in their tibiae and femurs. Jump-exercised rats, on the other hand, had significantly increased tibial bone mass, strength, and cortical areas. The bone mass and strength of OVX exercised rats increased to approximately the same extent as Sham exercised rats, despite estrogen deficiency or osteopenia. Our data suggest that jump exercise has beneficial effects on lower limb bone mass, strength, bone mineral density, and morphometry in middle-aged osteopenic rats, as well as in Sham rats.

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Comparative Effects of Er-Xian Decoction,EpimediumHerbs, and Icariin with Estrogen on Bone and Reproductive Tissue in Ovariectomized Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/241416 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 20

Author(s):

Liming Xue ◽

Yin Wang ◽

Yiping Jiang ◽

Ting Han ◽

Yan Nie ◽

...

Keyword(s):

Bone Resorption ◽

Tissue Level ◽

Ovariectomized Rats ◽

Protective Effects ◽

Reproductive Tissue ◽

Efficacy And Safety ◽

Menopausal Syndrome ◽

Treatment Of Osteoporosis ◽

Superior Efficacy ◽

Ovx Rats

Er-Xian Decoction (EXD),Epimediumherbs (herbs ofEpimedium brevicornumMaxim, EBH), and icariin (ICA) have been proven to have estrogen-like and antiosteoporotic activity and are used for the treatment of osteoporosis, menopausal syndrome, and age-associated diseases. The present study found that EXD, EBH, and ICA treatments, emulating estrogen, significantly contributed to bone density and architecture in OVX rats and that EXD is similar to estrogen and exerts a concomitant effect on bone formation and bone resorption at the tissue level, while EBH and ICA produced bone-protective effects mainly by inhibiting bone resorption. Nevertheless, EXD, EBH, and ICA treatments manifested a fewer adverse effects on the uterus, mammary gland, and vagina compared to estrogen administrations. Among the EXD, EBH, and ICA, EXD was found to have superior efficacy and safety profile.

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