Environmental Pollutant Tributyltin Shows Both Estrogenic and Adipogenic Activities in Metabolic, Reproductive and Coronary Tissue from Female Rats

Presentation Number: SAT 253
Date of Presentation: April 1st, 2017

Leandro C Freitas-Lima*1, Priscila Lang Podratz1, Eduardo Merlo1, Julia F P Araújo1, Gabriela Cavati Sena2, Idelson Gadioli santos Filho3, Amanda F. Z. Pereira4, Julia G M Ayub3, Adaliene V M Ferreira5, Marcelo G R Piñón6, Marina C Zicker3, Ian Victor Silva1, Celia T Bolon7, Roger L dos Santos8 and Jones B Graceli9
1Federal University of Espirito Santo, Vitoria, Brazil, 2Federal University of Espirito Santo, Vitória, BRAZIL, 3Universidade Federal do Espírito Santo, Brazil, 4Universidade Federal do Espírito Santos, 5Universidade Federal de Minas Gerais, Brazil, 6Universidad de la República, Uruguay, 7niversidad de la República, Uruguay, 8Federal University of Espirito Santo, Brazil, 9Federal University of Espirito Santo, Vitoria, BRAZIL


Tributyltin chloride (TBT) is an environmental pollutant used as a biocide that has been demonstrated to induce endocrine-disrupting effects, such as reproductive, metabolic and cardiovascular abnormalities. Obesity is associated with abnormal adiposity and inflammation, affecting the role of estrogen in the reproductive and cardiovascular function. However, studies that have investigated the estrogenic and adipogenic TBT effects in the adiposity, reproductive and coronary features are especially rare. Here, we describe the metabolic, sex hormonal profile and coronary characterization as result of TBT exposure in the ovarictomized female rats. To study whether TBT presented estrogenic and adipogenic activities, we performed the ovariectomy (OVX) and administered vehicle (OVX, 0.4% ethanol) and TBT (OVX+TBT, 100 ng/kg/day) in the Wistar female rats for 15 days via gavage. OVX and OVX+TBT rats displayed a similar body weight gain (p≥0.05; n=8-10), although an increase in the adiposity in OVX+TBT rats (OVX:0.023±0.001 vs OVX+TBT:0.033±0.003 g/g; p≤0.01; n=8-10). Serum triglyceride, cholesterol and glucose levels were similar between OVX and OVX+TBT rats (p≥0.05; n=8-10). No significant changes were observed in the serum leptin, adiponectin and resistin levels in OVX and OVX+TBT-fasted rats (p ≤ 0.05; n=8-10). However, increased values for the glucose tolerance test at 15 min (p ≤ 0.05; n=8-10) and pancreas weight (OVX:4.3±0.1 vs OVX+TBT:5.7±0.3 mg/g; p≤0.01; n=8-10) were identified in the OVX+TBT rats. No significant changes were observed in the serum estrogen, progesterone and testosterone levels in OVX and OVX+TBT (p ≥ 0.05; n=8-10). However, an increase in uterus weight was observed in the OVX+TBT rats (OVX:0.66±0.03 vs OVX+TBT:0.10±0.02 mg/g; p≤0.01; n=8-10). TBT was able to act as ligand the estrogen (OVX:1.47±0.13 vs OVX+TBT:2.44±0.28 fmol/mg tissue; p≤0.01; n=5) and progesterone (OVX:1.04±0.07 vs OVX+TBT:2.18 ±0.40 fmol/mg tissue; p≤0.05; n=5) receptor in uterine tissue from OVX+TBT rats using the saturation radioligand-binding assay. In coronary function assessment, TBT normalized a reduction in the coronary perfusion pressure (CPP) observed in the OVX rats (OVX:86.3±5.4 vs OVX+TBT:99.8±6.7 mm Hg; p≤0.05; n=8). The total vascular area, wall area and wall/ lumen ratio in the coronary arteries were similar between in OVX and OVX+TBT rats (p≥0.05; n=5). Thus, TBT disrupted estrogen proper functioning of the metabolic tissues, reproductive tract and coronary function, leading to abnormal estrogenic and adipogenic activities. This work supports the hypothesis that TBT impairs the normal estrogen role by acting in their receptor.