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

BACKGROUND/AIMS: Tributyltin (TBT) is an organotin (OTs) and biohazard organometallic pollutant. Recently our group has shown that TBT, even in very low doses, has deleterious effects on several tissues most likely due to its role as an endocrine-disrupting molecule. Other studies have confirmed that OT exposure could be responsible for neural, endocrine, and reproductive dysfunctions via in vitro and in vivo models. However, TBT effects on bone lack concise data despite the fact that bone turnover is regulated by endocrine molecules, such as parathormone (PTH), estrogen (E2), etc. Our group has already shown that TBT disrupts adrenal and female gonadal functions. METHODS: We studied the effects of TBT on bone metabolism and structure using DXA, microCT scan, and SEM. We also determined the calcium (Ca²âº) and phosphate (Pi) metabolism in TBT-treated rats as well as some biomarkers for bone formation and resorption. RESULTS: Surprisingly, we found that TBT leads to higher bone mineral density (BMD) although lesions in spinal bone were observed by either microCT scan or SEM. Biomarkers for bone resorption, such as the urinary deoxipyridinolines (DPD) excretion ratio was increased in TBT-treated animals versus mock-treated controls. Osteocalcin (OC) and alkaline phosphatase (AP) are markers of bone formation and are also elevated suggesting that the bone matrix suffers from a higher turnover. Serum Ca²âº (total and ionized) do not changed by TBT treatment although hypercalciuria is observed. CONCLUSION: It is known that Sn atoms have three valence states (Sn²âº, Sn³âº, and Sn4⁺); hence, we hypothesized that Sn (more likely Sn²âº) could be competing with Ca²âº and/or Mg²âº in hydroxyapatite mineral matrix to disturb bone turnover. Further work is needed to confirm this hypothesis.

Organotin Exposure and Vertebrate Reproduction: A Review.

Organotin (OTs) compounds are organometallic compounds that are widely used in industry, such as in the manufacture of plastics, pesticides, paints, and others. OTs are released into the environment by anthropogenic actions, leading to contact with aquatic and terrestrial organisms that occur in animal feeding. Although OTs are degraded environmentally, reports have shown the effects of this contamination over the years because it can affect organisms of different trophic levels. OTs act as endocrine-disrupting chemicals (EDCs), which can lead to several abnormalities in organisms. In male animals, OTs decrease the weights of the testis and epididymis and reduce the spermatid count, among other dysfunctions. In female animals, OTs alter the weights of the ovaries and uteri and induce damage to the ovaries. In addition, OTs prevent fetal implantation and reduce mammalian pregnancy rates. OTs cross the placental barrier and accumulate in the placental and fetal tissues. Exposure to OTs in utero leads to the accumulation of lipid droplets in the Sertoli cells and gonocytes of male offspring in addition to inducing early puberty in females. In both genders, this damage is associated with the imbalance of sex hormones and the modulation of the hypothalamic-pituitary-gonadal axis. Here, we report that OTs act as reproductive disruptors in vertebrate studies; among the compounds are tetrabutyltin, tributyltin chloride, tributyltin acetate, triphenyltin chloride, triphenyltin hydroxide, dibutyltin chloride, dibutyltin dichloride, diphenyltin dichloride, monobutyltin, and azocyclotin.