Dose-dependent effects of pharmaceutical treatments on bone matrix properties in ovariectomized rats

Prolongation of gastrointestinal transit resulting in nausea and vomiting in pregnancy (NVP) is the most common phenomenon during the first trimester of pregnancy. Increased human chorionic gonadotropin (hCG) concentration during the first trimester is the most likely cause of NVP. The aim of this study was to investigate the effect of hCG on gastrointestinal transit and plasma concentrations of cholecystokinin (CCK) in ovariectomized (Ovx) rats. I.p. injection of hCG was used to evaluate the dose effect of hCG on gastrointestinal transit in Ovx rats. The CCK antagonist lorglumide was used to clarify the role of CCK in regulating gastrointestinal transit. Gastrointestinal transit was assessed 15 min after intragastric gavage of a mixture of 10% charcoal and Na251CrO4(0.5 μCi/ml). After i.p. administration of hCG, gastric emptying was inhibited in Ovx rats, but intestinal transit was not affected. Plasma CCK concentrations were increased in a dose-dependent manner after hCG treatment, and gastric emptying showed a significant negative correlation with CCK concentrations (P=0.01,r2=−0.5104). Peripheral administration (i.p.) of lorglumide, a selective CCK1receptor antagonist, attenuated the hCG-induced inhibition of gastric emptying in Ovx rats, whereas central administration via the i.c.v. route did not. hCG treatment of Ovx rats inhibits gastric emptying in a dose-dependent manner via a peripheral mechanism of CCK hypersecretion and activation of CCK1receptors.

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Estradiol attenuates the antidiuretic action of vasopressin in ovariectomized rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.268.4.r951 ◽

1995 ◽

Vol 268 (4) ◽

pp. R951-R957 ◽

Cited By ~ 8

Author(s):

Y. X. Wang ◽

J. T. Crofton ◽

H. Liu ◽

K. Sato ◽

D. P. Brooks ◽

...

Keyword(s):

Slow Release ◽

Tap Water ◽

Female Rats ◽

Ovariectomized Rats ◽

Sexually Dimorphic ◽

Female Rat ◽

Ovarian Hormone ◽

Dose Dependent ◽

Antidiuretic Action

To determine which ovarian hormone is involved in the sexually dimorphic antidiuretic action of vasopressin, the antidiuretic response to vasopressin was examined in sham-operated nonestrous female rats chronically treated with vehicle and in ovariectomized rats treated with vehicle, progesterone, estradiol, or the combination of estradiol and progesterone, respectively. Three-week-old female rats were sham operated or ovariectomized, and a slow-release hormone pellet was implanted at the 6th wk. The experiment was performed at the 10th to 12th wk in conscious, chronically instrumented rats hydrated with tap water (2% body wt). Infusion of vasopressin at rates of 10-1,000 pg.min-1.kg body wt-1 resulted in a dose-dependent antidiuretic response that was significantly enhanced in ovariectomized rats compared with the intact nonestrous females. Progesterone had no effect, whereas estradiol attenuated and restored the antidiuretic response to vasopressin to a level similar to that in intact nonestrous female rats. These results suggest that it is estrogen, but not progesterone, that reduces the antidiuretic response to vasopressin in the female rat.

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Methanolic Extract of Ceplukan Leaf (Physalis minimaL.) Attenuates Ventricular Fibrosis through Inhibition of TNF-αin Ovariectomized Rats

Advances in Pharmacological Sciences ◽

10.1155/2016/2428052 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Bayu Lestari ◽

Nur Permatasari ◽

Mohammad Saifur Rohman

Keyword(s):

Heart Failure ◽

Treatment Group ◽

Wistar Rats ◽

Methanolic Extract ◽

Ovariectomized Rats ◽

Dependent Manner ◽

Estrogen Level ◽

Menopausal Women ◽

Ventricular Fibrosis ◽

Dose Dependent

The increase of heart failure prevalence on menopausal women was correlated with the decrease of estrogen level. The aim of this study is to investigate the effects of ceplukan leaf (Physalis minimaL.), which contains phytoestrogen physalin and withanolides, on ventricular TNF-αlevel and fibrosis in ovariectomized rats. Wistar rats were divided into six groups (control (—); OVX 5: 5-week ovariectomy (OVX); OVX 9: 9-week ovariectomy; treatments I, II, and III: 9-weeks OVX + 4-week ceplukan leaf’s methanolic extract doses 500, 1500, and 2500 mg/kgBW, resp.). TNF-αlevels were measured with ELISA. Fibrosis was counted as blue colored tissues percentage using Masson’s Trichrome staining. This study showed that prolonged hypoestrogen increases ventricular fibrosis (p<0.05). Ceplukan leaf treatment also resulted in a decrease of ventricular fibrosis and TNF-αlevel in dose dependent manner compared to without treatment group (p<0.05). Furthermore, the TNF-αlevel was normalized in 2500 mg/kgBWPhysalis minimaL. (p<0.05) treatment. The reduction of fibrosis positively correlated with TNF-αlevel (p<0.05,r=0.873). Methanolic extract of ceplukan leaf decreases ventricular fibrosis through the inhibition of ventricular TNF-αlevel in ovariectomized rats.

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The modified amino sugar N-Butyryl Glucosamine fed to ovariectomized rats preserves bone mineral through increased early mineralization, but does not affect body composition

Functional Foods in Health and Disease ◽

10.31989/ffhd.v7i10.377 ◽

2017 ◽

Vol 7 (10) ◽

pp. 795 ◽

Cited By ~ 1

Author(s):

Tassos Anastassiades ◽

Karen Rees-Milton ◽

Wilma M. Hopman

Keyword(s):

Body Composition ◽

Bone Mineral ◽

Bone Mineralization ◽

Bone Matrix ◽

Amino Sugar ◽

Dual Energy ◽

Ovariectomized Rats ◽

Mineral Density ◽

X Ray ◽

Ovx Rats

Background: The toxicities of pharmaceuticals for chronic arthritis and osteoporosis should be of concern to consumers. This partially accounts for the popularity of consumption of the amino sugar glucosamine, in-spite of controversy about its efficacy. We chemically synthesized N-butyryl glucosamine (GlcNBu), which we discovered protected bone and cartilage in an inflammatory arthritis rat model when used as a feed supplement. GlcNBu can also be potentially synthesized biochemically, since we recently demonstrated that human acetyl-CoA: glucosamine-6-phosphate N-acetyltransferase 1 has a relaxed donor specificity and transfers acyl groups of up to four carbons in length, i.e. the butyryl moiety. Oral GlcNBu had no detectable toxicity and also protected against bone loss in ovariectomized (OVX) rats as a model for osteoporosis. However, we demonstrated this only for bones excised at 6 months. Thus, the current study aims to determine when bone mineralization is maximized during daily GlcNBu supplementation, in both OVΧ and Sham-OVX rats, in addition to the relationship of bone mineralization to body composition.Methods: Female Sprague-Dawley rats were randomized into 4 groups, containing 8 rats each. The groups consisted of OVX or Sham-OVX rats whose diets were supplemented with either 200 mg/kg/day of GlcNBu or an equimolar amount of glucose. We performed sequential bone density and body composition measurements, by dual-energy X-ray absorptiometry in the live, anesthetised rats, over a 6-month experimental period, starting at the age of 8 weeks. Results were analyzed by descriptive statistics and 2-way ANOVA. Results: The major increases in the mineral content and density of the spine and the femur in GlcNBu-supplemented rats occurred early, from the baseline to week 8. Ovariectomy resulted in a number of significant differences in body composition, while feeding GlcNBu had no significant effects on body composition. The significant effects of ovariectomy on body composition initially appeared at 8 weeks, while the GlcNBu effects on increased bone mineral initially appeared at 2 weeks. An interaction between OVX and GlcNBu was seen only at 16 weeks for the bone mineral density of the femoral head.Conclusions: Supplementation of the diet by GlcNBu in both OVX and Sham-OVX rats increases bone mineral as early as 2 weeks. Ovariectomy but not GlcNBu supplementation had a significant effect on body composition. The effect of GlcNBu occurs independently of changes in body composition, probably as a direct effect of stimulation of bone matrix synthesis which continues to be mineralized. This work represents an important step in the development and commercialization of GlcNBu for the prevention and treatment osteoporosis, where there is now an increasing demand for safe, long term agents.Key words: osteoporosis, ovariectomy, N-butyryl glucosamine, bone, mineralization, body composition, dual-energy X-ray absorptiometry

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Control of Bone Matrix Properties by Osteocytes

Frontiers in Endocrinology ◽

10.3389/fendo.2020.578477 ◽

2021 ◽

Vol 11 ◽

Author(s):

Amy Creecy ◽

John G. Damrath ◽

Joseph M. Wallace

Keyword(s):

Type I Collagen ◽

Bone Matrix ◽

Type I ◽

Bone Homeostasis ◽

Surrounding Matrix ◽

Matrix Properties ◽

The Matrix ◽

Exciting Potential

Osteocytes make up 90–95% of the cellular content of bone and form a rich dendritic network with a vastly greater surface area than either osteoblasts or osteoclasts. Osteocytes are well positioned to play a role in bone homeostasis by interacting directly with the matrix; however, the ability for these cells to modify bone matrix remains incompletely understood. With techniques for examining the nano- and microstructure of bone matrix components including hydroxyapatite and type I collagen becoming more widespread, there is great potential to uncover novel roles for the osteocyte in maintaining bone quality. In this review, we begin with an overview of osteocyte biology and the lacunar–canalicular system. Next, we describe recent findings from in vitro models of osteocytes, focusing on the transitions in cellular phenotype as they mature. Finally, we describe historical and current research on matrix alteration by osteocytes in vivo, focusing on the exciting potential for osteocytes to directly form, degrade, and modify the mineral and collagen in their surrounding matrix.

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Endocytosis of Sugars in Embryonic Skeletal Tissues in Organ Culture

Journal of Cell Science ◽

10.1242/jcs.4.1.89 ◽

1969 ◽

Vol 4 (1) ◽

pp. 89-103

Author(s):

HONOR B. FELL ◽

J. T. DINGLE

Keyword(s):

Articular Cartilage ◽

Organ Culture ◽

Culture Medium ◽

Bone Matrix ◽

Fibrillar Structure ◽

Limb Bone ◽

Limb Bones ◽

Cartilage Cells ◽

Defined Culture ◽

Dose Dependent

The addition of sucrose to a chemically defined culture medium caused intense cytoplasmic vacuolation of the perichondrial, oesteogenic arid articular cartilage cells of limb-bone rudiments from 8½-day embryonic chicks grown in organ culture. The rest of the cartilage appeared unaffected by the sugar. The osteocytes were intensely vacuolated; the bone matrix was much less dense than that of the controls and had an abnormal fibrillar structure. When the explants were transferred to medium without sucrose, after 6 days vacuolation had almost disappeared. The effect of the sucrose was dose-dependent; at a concentration of 0.32M the sugar was highly toxic; at 0.16M the explants survived and vacuolation of the chondrocytes extended further into the cartilage than at 0.08M. A similar vacuolation of the cells in response to sucrose was seen in the isolated shafts of the limb-bones and in the mandibular rami from 11- to 13-day embryos; in the sucrose-treated explants osteogenesis was arrested and in places the bone showed osteolytic changes. In the absence of glucose, 8½-day limb-bone rudiments failed to grow and rapidly degenerated in medium containing 0.08 M sucrose, indicating that sucrose was very little if at all metabolized. Explants of 8½-day rudiments grown for 8 days in the presence of 0.8M glucose showed no vacuolation; dextran had some effect, and both mannitol and sorbitol caused vacuolation.

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Lipoic acid stimulates bone formation in ovariectomized rats in a dose-dependent manner

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2015-0439 ◽

2016 ◽

Vol 94 (9) ◽

pp. 947-954 ◽

Cited By ~ 2

Author(s):

Radoslaw Piotr Radzki ◽

Marek Bienko ◽

Dariusz Wolski ◽

Alicja Lis ◽

Agnieszka Radzka

Keyword(s):

Body Mass ◽

Lipoic Acid ◽

Experimental Treatment ◽

Physiological Saline ◽

Ovariectomized Rats ◽

Sham Operation ◽

Dependent Manner ◽

Skeletal Density ◽

Female Wistar Rats ◽

Dose Dependent

This study was undertaken to determine the osteotropic effect of different doses of lipoic acid (LA) on the mineralization of bone tissue in female Wistar rats with experimental osteopenia induced by bilateral ovariectomy. Fifty-six rats were randomly selected and submitted to either a sham operation (n = 8) or an ovariectomy (n = 48). The ovariectomized rats were randomly placed into two control groups, treated subcutaneously with either physiological saline or 17β-estradiol in the dose of 4 μg/kg body mass per day, and four experimental groups that received LA subcutaneously in the doses of 12.5, 25, 50, and 100 mg/kg body mass per day (n = 8 in each group). After 28 days of experimental treatment, the rats were sacrificed, and body mass, total skeletal density, and body composition were recorded. Blood serum and isolated femora were stored for further analysis. Our results revealed that the osteoprotective effect of LA was dose-dependent and was observed in rats treated with 50 and 100 mg/kg of LA. Moreover, the LA applied to the ovariectomized rats in the dose of 50 mg/kg not only stopped the bone resorption, but stimulated its formation.

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Increased strontium uptake in trabecular bone of ovariectomized calcium-deficient rats treated with strontium ranelate or strontium chloride

Journal of Synchrotron Radiation ◽

10.1107/s090904951103038x ◽

2011 ◽

Vol 18 (6) ◽

pp. 835-841 ◽

Cited By ~ 19

Author(s):

Bernhard Pemmer ◽

Jochen G. Hofstaetter ◽

Florian Meirer ◽

Stephan Smolek ◽

Peter Wobrauschek ◽

...

Keyword(s):

Trabecular Bone ◽

Calcium Intake ◽

Strontium Ranelate ◽

Bone Matrix ◽

Principal Component ◽

Ovariectomized Rats ◽

Strontium Chloride ◽

Radiation Induced ◽

Backscattered Electron ◽

Electron Imaging

Based on clinical trials showing the efficacy to reduce vertebral and non-vertebral fractures, strontium ranelate (SrR) has been approved in several countries for the treatment of postmenopausal osteoporosis. Hence, it is of special clinical interest to elucidate how the Sr uptake is influenced by dietary Ca deficiency as well as by the formula of Sr administration, SrRversusstrontium chloride (SrCl2). Three-month-old ovariectomized rats were treated for 90 days with doses of 25 mg kg−1d−1and 150 mg kg−1d−1of SrR or SrCl2at low (0.1% Ca) or normal (1.19% Ca) Ca diet. Vertebral bone tissue was analysed by confocal synchrotron-radiation-induced micro X-ray fluorescence and by backscattered electron imaging. Principal component analysis andk-means clustering of the acquired elemental maps of Ca and Sr revealed that the newly formed bone exhibited the highest Sr fractions and that low Ca diet increased the Sr uptake by a factor of three to four. Furthermore, Sr uptake in bone of the SrCl2-treated animals was generally lower compared with SrR. The study clearly shows that inadequate nutritional calcium intake significantly increases uptake of Sr in serum as well as in trabecular bone matrix. This indicates that nutritional calcium intake as well as serum Ca levels are important regulators of any Sr treatment.

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