Thalidomide affects the skeletal system of ovariectomized rats

Kaczmarczyk-Sedlak, Ilona; Folwarczna, Joanna; Trzeciak, Henryk I.

doi:10.1016/s1734-1140(09)70096-9

Cited by 11 publications

(8 citation statements)

References 38 publications

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“…Estrogen is the main sex hormone produced in females by the ovaries [52] , which induces uterine growth. Present data revealed a significant decrease in uterine weight and an increase in body weight ratio in estrogen deficient animals, which is in agreement with earlier studies [39,46] . The decline in the uterine weight ensured the success of the ovariectomy [52] .…”

Section: Effects On Bone Histopathologysupporting

confidence: 93%

“…Osteoporosis was induced in thirty rats by bilateral ovariectomy as follows: under ether anesthesia, a longitudinal incision was made inferior to the rib cage on the dorsolateral body wall and the ovaries were exteriorized, ligated and excised [39] . The remaining ten rats were subjected to sham operation using the same procedure except for the ligation and excision steps.…”

Section: Induction Of Osteoporosismentioning

confidence: 99%

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The antidepressant bupropion exerts alleviating properties in an ovariectomized osteoporotic rat model

et al. 2014

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Aim: depression is a risk factor for impaired bone mass and micro-architecture, but several antidepressants were found to increase the incidence of osteoporotic fractures. in the present study we used ovariectomized (oVX) rats as a model of osteoporosis to investigate the effects of the antidepressant bupropion on the femoral bones. Methods: oVX animals were treated with bupropion (30, 60 mg·kg -1 ·d -1 ) for six weeks. bone turnover biomarkers (urinary dPd/Cr ratio, serum BALP, OC, TRAcP 5b, CTX and sRANKL levels) and inflammatory cytokines (TNF-α, IL-1β and IL-6) were determined using ELISA. inductively coupled plasma mass spectroscopy (iCP-Ms) was used to determine the femoral bone mineral concentrations. The cortical and trabecular morphometric parameters of femoral bones were determined using micro-CT scan and histopathology. Results: In OVX rats, the levels of bone turnover biomarkers and inflammatory cytokines were significantly elevated and femoral bone Ca 2+ and Po 4 3-concentrations were significantly reduced. Moreover, cortical and trabecular morphometric parameters and histopathology of femoral bones were severely altered by ovariectomy. bupropion dose-dependently inhibited the increases in bone turnover biomarkers and inflammatory cytokines. OVX rats treated with the high dose of bupropion showed normal mineral concentrations in femoral bones. The altered morphometric parameters and histopathology of femoral bones were markedly attenuated by the treatment. Conclusion: bupropion exerts osteo-protective action in oVX rats through suppressing osteoclastogenesis-inducing factors and inflammation, which stabilize the osteoclasts and decrease bone matrix degradation or resorption.

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Section: Effects On Bone Histopathologysupporting

confidence: 93%

Section: Induction Of Osteoporosismentioning

confidence: 99%

The antidepressant bupropion exerts alleviating properties in an ovariectomized osteoporotic rat model

et al. 2014

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“…Similar changes in the ovariectomy rat model were previously observed [30, 45–47]. Estradiol supplementation caused withdrawal of some alterations connected with the uterus and body mass.…”

Section: Discussionsupporting

confidence: 84%

Effect of Formononetin on Mechanical Properties and Chemical Composition of Bones in Rats with Ovariectomy-Induced Osteoporosis

Kaczmarczyk-Sedlak

Wojnar

Zych

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Formononetin is a naturally occurring isoflavone, which can be found in low concentrations in many dietary products, but the greatest sources of this substance are Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, which all belong to Fabaceae family. Due to its structural similarity to 17β-estradiol, it can mimic estradiol's effect and therefore is considered as a “phytoestrogen.” The aim of this study was to examine the effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis. 12-week-old female rats were divided into 4 groups: sham-operated, ovariectomized, ovariectomized treated with estradiol (0.2 mg/kg) and ovariectomized treated with formononetin (10 mg/kg). Analyzed substances were administered orally for 4 weeks. Ovariectomy caused osteoporotic changes, which can be observed in bone biomechanical features (decrease of maximum load and fracture load and increase of displacements for maximum and fracture loads) and bone chemical composition (increase of water and organic fraction content, while a decrease of minerals takes place). Supplementation with formononetin resulted in slightly enhanced bone mechanical properties and bone chemistry improvement (significantly lower water content and insignificantly higher mineral fraction content). To summarize, administration of formononetin to ovariectomized rats shows beneficial effect on bone biomechanical features and chemistry; thus, it can prevent osteoporosis development.

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“…For instance, an antineoplastic agent (ATC code: L), thalidomide, was suggested for the treatment of osteoporosis, which is a musculoskeletal disease. This new therapeutic class for thalidomide was supported by earlier studies [41, 42]. …”

Section: Discussionmentioning

confidence: 73%

A phenome-guided drug repositioning through a latent variable model

et al. 2014

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BackgroundThe phenome represents a distinct set of information in the human population. It has been explored particularly in its relationship with the genome to identify correlations for diseases. The phenome has been also explored for drug repositioning with efforts focusing on the search space for the most similar candidate drugs. For a comprehensive analysis of the phenome, we assumed that all phenotypes (indications and side effects) were inter-connected with a probabilistic distribution and this characteristic may offer an opportunity to identify new therapeutic indications for a given drug. Correspondingly, we employed Latent Dirichlet Allocation (LDA), which introduces latent variables (topics) to govern the phenome distribution.ResultsWe developed our model on the phenome information in Side Effect Resource (SIDER). We first developed a LDA model optimized based on its recovery potential through perturbing the drug-phenotype matrix for each of the drug-indication pairs where each drug-indication relationship was switched to “unknown” one at the time and then recovered based on the remaining drug-phenotype pairs. Of the probabilistically significant pairs, 70% was successfully recovered. Next, we applied the model on the whole phenome to narrow down repositioning candidates and suggest alternative indications. We were able to retrieve approved indications of 6 drugs whose indications were not listed in SIDER. For 908 drugs that were present with their indication information, our model suggested alternative treatment options for further investigations. Several of the suggested new uses can be supported with information from the scientific literature.ConclusionsThe results demonstrated that the phenome can be further analyzed by a generative model, which can discover probabilistic associations between drugs and therapeutic uses. In this regard, LDA serves as an enrichment tool to explore new uses of existing drugs by narrowing down the search space.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2105-15-267) contains supplementary material, which is available to authorized users.

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Thalidomide affects the skeletal system of ovariectomized rats

Cited by 11 publications

References 38 publications

The antidepressant bupropion exerts alleviating properties in an ovariectomized osteoporotic rat model

The antidepressant bupropion exerts alleviating properties in an ovariectomized osteoporotic rat model

Effect of Formononetin on Mechanical Properties and Chemical Composition of Bones in Rats with Ovariectomy-Induced Osteoporosis

A phenome-guided drug repositioning through a latent variable model

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