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Influence of tamoxifen associated with chemotherapy on periimplant tissues

Grant number: 19/24825-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2021
Effective date (End): November 30, 2024
Field of knowledge:Health Sciences - Dentistry - Periodontology
Principal researcher:Juliano Milanezi de Almeida
Grantee:Luiz Guilherme Fiorin
Home Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

The purpose of the present study will be to evaluate the bone remodeling of osseointegrated implants installed in tibias of rats modified or not systemically by tamoxifen associated or not to Cisplatin (CIS) or 5-Fluorouracil (5-FU. 252 rats will be used, the animals will receive ovariectomy bilaterally (OVX), tibial implant placement bilaterally and after 6 weeks will be randomized into two large groups (n = 108), which will receive 0.5 ml saline (SS) and 15mg/kg tamoxifen citrate (TAM) throughout the experimental period and then in three subgroups (n=36) according to the antineoplastic agents: CIS, 5-FU or 0.5 ml SS antineoplastic agents were administered. intraperitoneally, within 48 h between applications, for CIS 5 mg/kg and 2.5 mg/kg, and for 5 FU 60 mg/kg and 40 mg/kg respectively. in a negative control group total who will not receive ovariectomy and will receive only SS via gavage and intraperitoneal (SHAM) (n=36). SHAM + SS-SS: gavage SS administration throughout the experimental period and 2 doses of intraperitoneal saline. OVX + SS-SS group: gavage SS administration throughout the experimental period and 2 doses of intraperitoneal saline. OVX + SS-CIS group: gavage administration of 0.5 ml 0.9% saline over the entire experimental period and 2 doses of intraperitoneal cisplatin. OVX + SS-5-fu group: gavage administration of 0.5 ml 0.9% saline throughout the experimental period and 2 doses of intraperitoneal 5-Fluorouracil. OVX + TAM-SS Group: tamoxifen gavage administration throughout the experimental period and 2 doses of intraperitoneal SS. OVX + TAM-CIS Group: gavage administration of tamoxifen throughout the experimental period and 2 doses of intraperitoneal cisplatin. OVX + TAM-5-fu group: tamoxifen gavage administration throughout the experimental period and 2 doses of intraperitoneal 5-Fluorouracil. Twelve animals from each group will be euthanized at week 10, 14 and 18, the tibias will be collected and fixed in 4% buffered formaldehyde for 48h and randomly assigned to processing without demineralization for bone/implant contact analysis (COI) or demineralization processing and paraffin inclusion for histometric analysis of percentage of newly formed bone tissue (PTON), histological and immunohistochemistry for detection of BMP2/4, RUNX2, OCN and TRAP. Other specimens will be fixed in 2.5% glutaraldehyde and 0.1M cacodylate buffer for ultrastructural analysis of Scanning Electron Microscopy (SEM) and elemental X-ray spectroscopy dispersion (EDS). (AU)

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