As 2-hidroxi-3,4,6-trimetoxifenilchalconas protegem as células tubulares renais contra os danos oxidativos e inflamatórios causados pela cetamina : possível envolvimento das vias JNK/46A e MAPK/CJA

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Cavalcanti, Mariana Maciel
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/71329
Resumo: Drug-induced nephrotoxicity is one of the causes of acute kidney injury (AKI), where drugs such as ketamine can cause kidney damage through cell death and oxidative stress. In view of the process of alteration of the oxide-reductive balance and cell death produced by this drug, it is important to study molecules capable of regulating the production of reactive oxygen species (ROS), such as chalcones. These anti-inflammatory and antioxidant molecules, present in Brazilian biodiversity, allow the optimization of their structures, improving their pharmacological activity. The objective of this work was to evaluate the cytoprotective effect of 2-hydroxy-3,4,6-trimethoxyphenylchalcone (HTMCX), from the species Croton anisodontus Müll.Arg, against tubular cell damage induced by ketamine and to compare its effect with the their semi-synthetic chalcones. HK-2 cells were treated with non-toxic concentrations of chalcones (31.25 µM and 15.62 µM) and/or Ketamine IC50 (2.55 mM). Cell viability was assessed by the MTT assay. Flow cytometry was used to assess cell death, oxidative stress and mitochondrial transmembrane potential. Parameters that evaluate the oxide-reductive balance (SOD and GSH), Kidney Injury Molecule 1 (KIM-1) and inflammatory biomarkers (IL-6 and IFN-ɣ) were determined. Ultrastructural changes were observed by scanning electron microscopy. Finally, molecular docking tests were carried out with possible pathways of action of the molecules under study. Treatment with HTMCX and its semi-synthetic chalcones, among which CPN2F stands out, improved cell viability after lesion induction with Ketamine, with a reduction in apoptosis and KIM-1 release. This was associated with a partial attenuation of morphological changes, being related to an antioxidant and protective effect on mitochondria. Chalcones reduced ketamine-induced production of pro-inflammatory cytokines in cells. These effects seem to be related to the binding of chalcones to proteins in the JNK/p38 MAPK pathway.