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Cytoprotective effect of Arrabidaea chica Verlot extract associated with a fraction enriched with geranylgeraniol from Bixa orellana L. in epithelial cells treated with bisphosphonate

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Author(s):
Machado Júnior, Rogério José
Total Authors: 1
Document type: Master's Dissertation
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Abstract

Bisphosphonates are drugs widely used for the treatment of bone diseases such as osteoporosis and bone metastases. Despite their clinical importance, the chronic use of these medications is associated with the occurrence of medication-induced maxillary osteonecrosis, such as bisphosphonates. The lesion is rare, but of great morbidity and difficult to control. Based on studies that found that geranylgeraniol replacement, inhibited by bisphosphonates, or in vitro cell treatment with Arrabidaea chica Verlot (A. chica) extract demonstrated promising effects for the treatment of osteonecrotic condition, the aim of this work was to evaluate the effects cytoprotectors from A. chica extract associated with a fraction enriched with geranylgeraniol from Bixa orellana, in epithelial cells exposed to zoledronic acid (bisphosphonate). Keratinocytes (HaCaT) were exposed, in vitro, to the deleterious effects of 50 µM zoledronic acid (ZA). At the same time, the cells were treated with concentrations of 5 and 1 µg / mL of A. chica (AC) associated with fraction enriched with geranylgeraniol 1, 7 and 15 µg / mL (GG) for 24, 48 and 72 hours. After this period, the cells were subjected to viability analysis (via the MTT reagent), the levels of the pro-inflammatory cytokine IL-1ß, evaluation of the clonogenic potential and evaluation of the antiproliferative activity. The data obtained were tabulated and submitted to analysis of variance considering a significance level of 5%. In the cell viability assay, the treatments ZA + AC1 + GG15 and ZA + AC5 + GG15 proved to be promising in the preservation of cells, with viability values of 73.5% and 71.1%, respectively. As for the dosage of the IL-1ß cytokine, it was not identified in the evaluated samples, emphasizing the importance of future analyzes. In the evaluation of the clonogenic potential, it was possible to observe that in the long term, the ZA + AC5 + GG15 treatment provided the evaluated strain with 96% of surviving fraction. In addition, in the antiproliferative activity evaluation test, none of the evaluated treatments showed proliferative or antiproliferative action on the evaluated cell line, demonstrating safety in the use of the investigated treatments. Thus, the concentrations of AC 1 and 5 µg / mL and GG 15 µg / mL when combined, showed promise in the treatment of osteonecrosis lesions caused by 50 µM ZA, demonstrating a possible synergistic effect between these compounds. Further studies will be necessary to prove the action of these compounds in other cells that involve the healing process, as well as the evaluation of their behavior in vivo, for a possible development of a phytotherapic with cytoprotective actions that can assist in the treatment of maxillary osteonecrosis lesions drug-induced. (AU)

FAPESP's process: 18/20252-8 - Evaluation of the association of extracts of Pterodon pubescens Benth., Arrabidaea chica Verlot and Bixa orellana fruits in healing, antinociceptive and anti-inflammatory activities
Grantee:Mary Ann Foglio
Support type: Regular Research Grants