scholarly journals Intermittent administration sodium valproate has a protective effect on bone health in ovariectomized rats

Author(s):  
Zhoushan Tao

Abstract Objective: the present work was aimed to evaluate the effect of different administration modes of sodium valproate(VPA) on bone strength, bone mass and bone mineral density in ovariectomized(OVX) rats and further investigation of the possible mechanism. Methods: 60 female SD rats were randomly divided into 4 groups: Sham group (Sham, n=15), OVX group (OVX, n=15), OVX rats received intermittent VPA treatment group(IVPA, n=15) and OVX rats received daily VPA treatment group(EVPA, n=15). After 12 weeks of treatment, the rats were sacrificed, and serum and femur samples were harvested. DEXA, Micro-CT, histology, biomechanical testing, biochemical index and western blot analysis were used to observe the therapeutic effect and explore the possible mechanism. Results: Micro-CT and DEXA analysis of bones revealed better BMD and higher BV/TV, Tb.Th, Tb.N, Conn. D and lower Tb.Sp at femoral metaphysis with evaluated in IVPA when compared with OVX and EVPA group(P<0.05). Histological, fluorescent analysis and biological strength revealed more trabecular bone and higher relative mineral apposition rate, maximal load, elastic modulus and energy at break with evaluated in IVPA when compared with OVX and EVPA group(P<0.05). The levels of P1NP, estrogen, CTX, TRAP5b and RANKL of IVPA group showed a significant increase when compared with the OVX and EVPA group(P<0.05). We confirm adverse effects on protein expressions including Notch1, Jagged1, HEY1, Wnt 1, β‐catenin and RUNX2 following daily VPA treatment in OVX female rats. Conclusions: Our current study demonstrated that intermittent administration sodium valproate has a protective effect on bone health in ovariectomized rats and these effects may be achieved by activating Notch/Wnt/β-catenin/ RUNX2 signal axis.

2001 ◽  
Vol 86 (4) ◽  
pp. 521-527 ◽  
Author(s):  
Joseé Gala ◽  
Manuel Di´az-curiel ◽  
Concepcioó de la Piedra ◽  
Jesu´s Calero

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.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Zhiguo Zhang ◽  
Jiazi Dong ◽  
Meijie Liu ◽  
Yan Li ◽  
Jinghua Pan ◽  
...  

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.


2003 ◽  
Vol 95 (3) ◽  
pp. 1032-1037 ◽  
Author(s):  
Akiko Honda ◽  
Naota Sogo ◽  
Seigo Nagasawa ◽  
Takuya Shimizu ◽  
Yoshihisa Umemura

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.


Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2943
Author(s):  
Hui-Hui Xiao ◽  
Xueli Yu ◽  
Chen Yang ◽  
Chi-On Chan ◽  
Lu Lu ◽  
...  

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.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Chun Lei Li ◽  
Xi Ling Liu ◽  
Wei Xin Cai ◽  
Weijia William Lu ◽  
Roger A. Zwahlen ◽  
...  

Objective.Technically primates and dogs represent ideal models to investigate diseases characterized by abnormal intracortical remodeling. High expenses and ethical issues, however, restrict the use of those animals in research. Rodent models have been used as alternatives instead, but their value is limited, if none, because these animals lack intracortical bone remodeling. This study aimed at investigating the effect of ovariectomy onto the stimulation of intracortical remodeling in rat mandibles.Materials and Methods.Sixteen 12-week-old Spraque-Dawly (SD) female rats were randomly assigned into two groups, receiving either ovariectomy or sham operation. All the rats were sacrificed 18 weeks postoperatively. The entire mandibles were harvested for microcomputed tomography (micro-CT) and histomorphometric assessments.Results.Micro-CT examination showed significantly decreased bone mineral density (0.95 ± 0.01 versus 1.01 ± 0.02 g/cm3,P<0.001) and bone volume (65.78 ± 5.45 versus 87.41 ± 4.12%,P<0.001) in ovariectomy group. Histomorphometric assessment detected a sixfold increased intracortical bone remodeling as well as an increased bone modeling in mandibles of ovariectomized rats.Conclusion.For the first time, to the authors’ knowledge, it was detected that ovariectomy stimulates intracortical remodeling in rat mandibles. This animal model might be of use to study various bone diseases associated with an abnormal intracortical remodeling process.


2007 ◽  
Vol 103 (2) ◽  
pp. 524-533 ◽  
Author(s):  
N. Bonnet ◽  
N. Laroche ◽  
H. Beaupied ◽  
L. Vico ◽  
E. Dolleans ◽  
...  

Previous studies in healthy rats have demonstrated a deleterious bone impact of β-agonist treatment. The purpose of this study was to examine the trabecular and cortical effects of β2-agonists at doping dose on treadmill exercising rats with estrogen deficiency. Adult female rats were ovariectomized (OVX; n = 44) or sham operated ( n = 12). Then, OVX rats received a subcutaneous injection of salbutamol (SAB) or vehicle with (EXE) or without treadmill exercise for 10 wk. Bone mineral density (BMD) was analyzed by densitometry. Microcomputed tomography and histomorphometric analysis were performed to study trabecular bone structure and bone cell activities. After 10 wk, SAB rats presented a much more marked decrease of BMD and trabecular parameters. Exercise did not change the high level of bone resorption in OVX EXE SAB compared with OVX SAB group (both on COOH-terminal collagen cross-links and osteoclast number). These results confirm the deleterious effect of β2-agonists on bone quantity (femoral BMD gain: OVX EXE, +6.8%, vs. OVX EXE SAB, −1.8%; P < 0.01) and quality (−8.0% of femoral trabecular thickness in OVX EXE SAB vs. OVX EXE), indicating that SAB suppresses the effect of EXE in OVX rats. Furthermore, we notice that the slight beneficial effect of exercise was mainly localized in the tibia. These findings indicate the presence of a bone alteration threshold below which there is no more alteration in structural bone quantity and quality. The negative effects of SAB on bone observed in this study in trained rats may indicate potential complications in doping female athletes with exercise-induced amenorrhea.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mercedes Montero ◽  
Manuel Díaz-Curiel ◽  
David Guede ◽  
Jose Ramón Caeiro ◽  
Marta Martín-Fernández ◽  
...  

We studied the ability of Kalsis, a food supplement that contains selenium, citric acid, and vitamin E, to prevent the effects of ovariectomy on bone loss. Six-month-old, Wistar female rats were studied. Groups (n=12): SHAM: sham-operated rats; OVX: ovariectomized rats, treated with vehicle; OVX + Kalsis: ovariectomized rats treated with Kalsis (25 mg/kg/day) for 3 months. Bone mineral density (BMD) was determined by DXA in lumbar spine and femur. Computerized microtomography (μCT) in femur and serum osteocalcin (BGP), aminoterminal propeptide of procollagen I (PINP),β-isomer of carboxyterminal telopeptide of collagen I (CTX), and 5b isoenzyme of tartrate-resistant acid phosphatase (TRAP) were performed. Treatment with Kalsis prevented BMD loss in OVX group.μCT showed a decrease in BV/TV, and trabecular number, and an increase in trabecular separation in OVX rats. Kalsis administration attenuated partially bone loss observed byμCT due to ovariectomy. BGP, PINP, and the resorption index (CTX/TRAP) were increased in OVX group. Treatment with Kalsis maintained this increase. The mechanism of action of this supplement is not through a decrease in bone remodelling rate. The antioxidant action of this food supplement, due to the synergism of all its components, as a cause of its beneficial effect is suggested.


2011 ◽  
Vol 212 (2) ◽  
pp. 179-186 ◽  
Author(s):  
Rana Samadfam ◽  
Malaika Awori ◽  
Agnes Bénardeau ◽  
Frieder Bauss ◽  
Elena Sebokova ◽  
...  

Peroxisome proliferator-activated receptor (PPAR) γ agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARα agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10 mg/kg per day)+Feno (25 mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ∼50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (∼45%) and bone mineral density (BMD; ∼60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARγ and PPARα may reduce the negative effects of PPARγ agonism on bone mass.


BioMedicine ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 8 ◽  
Author(s):  
Dimitrios Galanis ◽  
Konstantinos Soultanis ◽  
Pavlos Lelovas ◽  
Alexandros Zervas ◽  
Panagiotis Papadopoulos ◽  
...  

Objective: The aim of this study was to evaluate the potential effect of the methanolic extract of plantGlycyrrhiza glabraroots on bone mineral density and femoral bone strength of ovariectomized rats.Methods: Thirty 10-month-old Wistar rats were randomly separated into three groups of ten, Control, Ovariectomy and Ovariectomy-plus-Glycyrrhiza in their drinking water. Total and proximal tibial bone mineral density was measured in all groups before ovariectomy (baseline) and after 3 and 6 months post ovariectomy. Three-point-bending of the femurs and uterine weight and histology were examined at the end of the study.Results: No significant difference was noted in bone density percentage change of total tibia from baseline to 3 months between Control and Ovariectomy-plus-Glycyrrhiza groups (+5.31% ± 4.75 and +3.30% ± 6.31 respectively,P = non significant), and of proximal tibia accordingly (+5.58% ± 6.92 and +2.61% ± 13.62,P = non significant) demonstrating a strong osteoprotective effect. There was notable difference in percentage change of total tibia from baseline to 6 months between groups Ovariectomy and Ovariectomy-plus-Glycyrrhiza (−13.03% ± 5.11 and −0.84% ± 7.63 respectively,P < 0.005), and of proximal tibia accordingly (−27.9% ± 3.69 and −0.81% ± 14.85 respectively,P < 0.001), confirming the protective effect ofGlycyrrhiza glabraextract in preserving bone density of the Ovariectomy-plus-Glycyrrhiza group. Three-point-bending did not reveal any statistically significant difference between Ovariectomy and Ovariectomy-plus-Glycyrrhiza groups. Uterine weights of the Ovariectomy-plus-Glycyrrhiza group ranged between the other two groups with no statistically significant difference to each.Conclusions:Glycyrrhiza glabraroot extract notably protected tibial bone mineral density loss in Ovariectomy-plus-Glycyrrhiza rats in comparison with ovariectomized rats, but did not improve biomechanical strength.


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