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Resveratrol role on modulation of Aryl-hydrocarbon receptor (AhR) and on prostate development in rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy.

Grant number: 13/04401-0
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): June 01, 2013
Effective date (End): February 28, 2015
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Wellerson Rodrigo Scarano
Grantee:Lívia Teresa Ribeiro da Silveira
Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


Nowadays, TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a dioxin like compound, is considered the most toxic environmental contaminant with great relevance for studies involving human and animal health. Its action is associated by the interaction with the aryl hydrocarbon receptor (AhR), responsible for the biological effects of TCDD on the cells. Regarding to the prostate, AhR modulates the inhibitory effects of TCDD in the growth and maintenance of prostatic structure. Resveratrol is notable for its anticancer, antiplatelet aggregation, anti-inflammatory and antiallergic properties, besides its potent antioxidant and estrogenic activities, including antagonist function of AhR. This project aims to: 1) evaluate whether resveratrol is able to alter the effect of gestational exposure to TCDD through the aryl-hydrocarbon receptor pathway, 2) evaluate the effects of early and late gestational exposure to TCDD and resveratrol by morphological and molecular parameters, 3) analyze the cellular turnover using the processes of cell proliferation and cell death, 4) investigate the regulatory proteins of cellular stress pathways; 5) examine the hormone receptors expression involved in the development and maintenance of the prostate. Thus, pregnant females Sprague-Dawley will be divided into 4 groups: Control, TCDD, TCDD+resveratrol and resveratrol. The TCDD will be given as a single dose on the gestacional day 15 (GD 15) at 1µg/kg and resveratrol will be administered between DG10 and DG21 at 20mg/kg, both via gavage. The TCDD will be diluted in DMSO and resveratrol in carboxymethylcellulose, which constitute the vehicle dilution. Newborn males (PND1) will be euthanized for evaluation of TCDD immediate effects (with or without the addition of resveratrol) on the morphogenesis of the prostate, by morphological and immunohistochemical techniques. On PND90, males will be euthanized, blood will be collected for hormone dosage, the prostate complex will be removed and submittted to morphological, immunohistochemical and molecular techniques. Stereological analyzes to measure the teciduals constituents volume, count of p63-positive basal cells and the cell proliferation index will be realized.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RIBEIRO SILVEIRA, LIVIA TERESA; SANTOS, TALITA DE MELLO; CAMORA, LUCAS FREDINI; PINHO, CRISTIANE FIGUEIREDO; ANSELMO-FRANCI, JANETE A.; DOMENICONI, RAQUEL FANTIN; JUSTULIN, LUIS ANTONIO; BARBISAN, LUIS FERNANDO; SCARANO, WELLERSON RODRIGO. Protective effect of resveratrol on urogenital sinus and prostate development in rats exposed in utero to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). REPRODUCTIVE TOXICOLOGY, v. 83, p. 82-92, . (13/04401-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVEIRA, Lívia Teresa Ribeiro da. Papel do resveratrol sobra a modulação do receptor Aril-hidrocarboneto (AhR) e o desenvolvimento da próstata de ratos expostos ao 2, 3, 7, 8-tetraclorodibenzo-p-dioxina (TDCC) durante a gestação. 2015. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.

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