Protective effect of endoplasmic reticulum stress inhibition on 5-fluorouracil-induced oral mucositis.
Eur J Pharmacol
; 919: 174810, 2022 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-35151644
5-Fluorouracil (5-FU)-induced oral mucositis has a severe negative impact on the patient's quality of life. This study aimed to investigate the role of endoplasmic reticulum stress (ERS) in the occurrence of 5-FU-induced oral mucositis in vivo and in the clinic. In vivo, 5-FU-induced oral mucositis model mice showed a higher level of glucose-regulated protein 78 kD (GRP78, a marker of ERS) than control mice. The inhibition of ERS could effectively reduce 5-FU-induced oxidative stress, inflammatory factor mRNA and cell apoptosis. Moreover, inhibition of ERS significantly decreased the activation of nuclear factor kappa-B (NF-κB) in 5-FU-induced oral mucositis model mice following tissue damage reduction. In the clinic, 5-FU could increase cell apoptosis and cause oral mucosa damage while increasing the expression of the ERS marker genes GRP78 and C/EBP-homologous protein (CHOP). Our study found that 5-FU could induce severe ERS, upregulate the expression of GRP78 and CHOP, raise oxidative stress and increase the expression of inflammatory factors by activating the NF-κB pathway, thus causing cell apoptosis and finally leading to oral mucosal injury.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenilbutiratos
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Estomatite
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Estresse do Retículo Endoplasmático
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article