Banca de DEFESA: HENRIQUE RODRIGUES DE OLIVEIRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : HENRIQUE RODRIGUES DE OLIVEIRA
DATE: 19/12/2022
TIME: 14:00
LOCAL: Plataforma Teams
TITLE:

EVALUATION OF THE POTENTIAL NEUROPROTECTIVE EFFECT OF AQUEOUS EXTRACT OF Eugenia dysenterica DC IN A MODEL OF PERIPHERAL NEUROPATHY INDUCED BY CISPLATIN in vitro

KEY WORDS:

Chemotherapy-induced peripheral neuropathy; cisplatin; neuroprotection; oxidative stress; CGRP; IL-1b; Eugenia dysenterica

PAGES: 100
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

Chemotherapy-induced peripheral neuropathy (CIPN) is a clinical manifestation of several classes of antitumor drugs, such as platinum derivatives. Cisplatin is an antitumor widely used in oncology practice due to its ability to induce apoptosis in tumor cells as a result of the formation of platinum adducts in DNA. However, in neurons, cisplatin induces changes that will culminate in peripheral neuropathy, a set of symptoms characterized by being predominantly sensory and dose-dependent. Among these symptoms are paresthesia, sensory loss and neuropathic pain, which can be acute or chronic. These effects occur because the neurons of the dorsal root ganglia (DRGs) are the targets of these drugs. Given this, developing strategies aimed at protecting the nervous system is essential for CIPN treatment. Thus, the purpose of this work is to evaluate in vitro whether aqueous extract of Eugenia dysenterica leaves (plant from Cerrado popularly known as Cagaita) has a neuroprotective role in the CIPN model. These hypotheses are supported due to the antioxidant and anti-inflammatory activities of this plant, in addition to the neuroprotective effect already demonstrated in other neurotoxicity models. Thus, primary cultures of DRG cells from adult rats and neuron-like PC-12 cells were established, which were treated with E. dysenterica extract in the presence or absence of cisplatin. The effects of these treatments on cisplatin neurotoxicity were evaluated using the techniques of evaluating cell viability, quantification of calcitonin gene-related peptide (CGRP) release and quantification of total CGRP, quantification of mRNA for Superoxide dismutase 2 (SOD2) and NRF2, the release of Interleucin-1b (IL-1b), the synthesis of reactive oxygen species and the measurement of neurites. We observed that treatment with 30 µM cisplatin for 24 hours did not induce cell death in DRG cells, increased neuronal sensitization and induced oxidative stress in PC-12 cells, which were prevented by pretreatment with 30 µg/mL of E. dysenterica extract. Furthermore, we observed that cisplatin promotes increased IL-1b release, SOD-2 gene synthesis and inhibition of neurite outgrowth. On the other hand, treatment only with 30 µg/mL of E. dysenterica extract also does not alter the cell viability of DRG cells, IL-1b release and SOD-2 gene expression, however it reduces Nrf2 expression. Furthermore, we observed that the extract does not interfere with the cisplatin antitumor activity or its effect on neurites. We also observed that Nrf2/Keap1/ARE pathway activators, oltipraz and sulforaphane, induced neuronal sensitization. In summary, our data demonstrate that E. dysenterica extract can be a promising tool for the treatment of cisplatin-induced PN.

BANKING MEMBERS:
Externa à Instituição - JOICE MARIA DA CUNHA - UFPR
Externa à Instituição - REGINA DE CASTRO ALMEIDA - UFPI
Externa ao Programa - 2532427 - DAYDE LANE MENDONCA DA SILVA
Externa ao Programa - 1709601 - FABIANE HIRATSUKA VEIGA
Presidente - 186.580.591-20 - FRANCISCO DE ASSIS ROCHA NEVES - UNIFESP