Effects of Tributyltin (TBT) on Rat Bone and Mineral Metabolism

Resgala, Ludmilla Carvalho Rangel; Santana, Higor Scardini; Portela, Bruna Souza Mendonça; Zanovello, Maria Victória Souza; Costa, Charles S. da; Niño, Oscar; Bicudo, Nicolle Endlich; Santos, Diandra Zipinotti dos; Podratz, Priscila L.; Cunha, Maura Da; Oliveira, André Lacerda de Abreu; Freitas-Lima, Leandro Ceotto; Gomes-Rochette, Neuza Felix; Rangel, Letícia Batista Azevedo; Graceli, Jones Bernardes; Silva, Ian Victor

doi:10.33594/000000079

Cited by 10 publications

(2 citation statements)

References 29 publications

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“…In contrast, TBT significantly (i.e., there was a significant interaction) mitigated OVX-mediated reductions in trabecular bone volume fraction, trabecular number and trabecular spacing, along with a modest mitigation of OVX-mediated reduction in connective density. These results and the observation that TBT induced an increase in whole body bone mineral density [27] provide independent corroboration of our previous observation that TBT treatment can increase trabecular bone.…”

Section: Discussionsupporting

confidence: 91%

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Tributyltin Protects Against Ovariectomy-Induced Trabecular Bone Loss in C57BL/6J Mice with an Attenuated Effect in High Fat Fed Mice

Freid

Hussein

Schlezinger

2021

Preprint

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Risk factors for poor bone quality include estrogen loss at menopause, a high fat diet and exposures to drugs/chemicals that activate peroxisome proliferator activated receptor gamma (PPARγ). We observed that the PPARγ and retinoid X receptor dual ligand, tributyltin (TBT), repressed periosteal bone formation but enhanced trabecular bone formation in female C57BL6/J mice. Here, we examined the interaction of diet, ovariectomy (OVX) and TBT exposure on bone structure. C57BL/6J mice underwent either sham surgery or OVX at 10 weeks of age. At 12 weeks of age, they were placed on a low (10% kcal) or high (45% kcal) fat, sucrose-matched diet and treated with Vh or TBT (1 or 5 mg/kg) for 14 weeks. OVX increased body weight gain in mice on either diet. TBT enhanced body weight gain in intact mice fed a high fat diet, but decreased weight gain in OVX mice. Elemental tin concentrations increased dose-dependently in bone. TBT had marginal effects on cortical and trabecular bone in intact mice fed a low- or high-fat diet. OVX caused a reduction in cortical and trabecular bone, regardless of diet. In high-fat fed OVX mice, TBT further reduced cortical thickness, bone area and total area. Interestingly, TBT protected against OVX-induced trabecular bone loss in low fat fed mice. The protective effect of TBT was nullified by the high fat diet and accompanied by a significant decrease in serum bone formation markers. Our novel observations will provide new information on basic bone biology, potential therapeutic targets and toxicological pathways.

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Section: Discussionsupporting

confidence: 91%

“…In young, female C57BL/6 mice, exposure to TBT reduces periosteal bone formation but increases trabecular bone formation [26]. This is consistent with observations in young female rats in which TBT induced an increase in whole body bone mineral density [27].…”

Section: Introductionsupporting

confidence: 86%

Tributyltin Protects Against Ovariectomy-Induced Trabecular Bone Loss in C57BL/6J Mice with an Attenuated Effect in High Fat Fed Mice

Freid

Hussein

Schlezinger

2021

Preprint

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Low-dose tributyltin triggers human chondrocyte senescence and mouse articular cartilage aging

et al. 2022

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Current Evidence on the Effects of Endocrine-Disrupting Chemicals (EDCs) on Bone Growth and Health

Shulhai,

Palanza,

Street

2023

Expo Health

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Endocrine-disrupting chemicals (EDCs) are a heterogeneous group of natural and man-made chemicals from environmental sources that mimic natural hormones. They can have adverse effects on the morphology, physiology, growth, and development of different organs and systems, among these bone health can be affected too. EDCs work as agonists or antagonists on hormonal receptors in hormone-sensitive cells, influence gene expression by epigenetic mechanisms, stimulate or inhibit cell maturation, and affect the synthesis and metabolism of hormones. This review aims to summarize current evidence on the effects of exposure to EDCs on bone from early gestational to birth and long-term adverse effects. Single and mixtures of endocrine-disrupting chemicals can disrupt bone structure by modifying differentiation, increasing osteoclast activity, inhibiting pre-osteoblasts differentiation into mature osteoblasts and osteocytes, inducing changes in signaling pathways downstream of receptors, and ultimately remodeling and modifying the equilibrium between bone resorption and formation leading to increased bone resorption, morphological, and functional changes in bone maturation. EDCs can affect the IGF system, alkaline phosphatase, and osteocalcin gene expression. Findings are relative to both in vitro and in vivo studies. Studies have shown that prenatal exposure to EDCs leads to growth retardation, delayed ossification, and changes in bone length and size and in bone geometry with a lowering of bone mineral density and area-adjusted bone mineral content. Current knowledge on bone health, growth, mineral content, and development from molecular to clinical findings highlights how endocrine-disrupting chemicals can negatively affect these processes. Mechanisms, however, are not fully understood and need further investigation.

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Effects of Tributyltin (TBT) on Rat Bone and Mineral Metabolism

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 10 publications

References 29 publications

Tributyltin Protects Against Ovariectomy-Induced Trabecular Bone Loss in C57BL/6J Mice with an Attenuated Effect in High Fat Fed Mice

Tributyltin Protects Against Ovariectomy-Induced Trabecular Bone Loss in C57BL/6J Mice with an Attenuated Effect in High Fat Fed Mice

Low-dose tributyltin triggers human chondrocyte senescence and mouse articular cartilage aging

Current Evidence on the Effects of Endocrine-Disrupting Chemicals (EDCs) on Bone Growth and Health

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