Oltipraz attenuated cerebral ischemia-reperfusion injury through inhibiting the oxidative stress and ferroptosis in mice.
Int Immunopharmacol
; 140: 112800, 2024 Oct 25.
Article
em En
| MEDLINE
| ID: mdl-39096875
ABSTRACT
Oltipraz (OPZ) is a synthetic dithiolethione and is considered a novel activator of nuclear factor E2-related factor 2 (Nrf2). Increasing evidence indicates that Nrf2 protects against cerebral ischemia/reperfusion (I/R) injury by antagonizing ferroptosis and lipid peroxidation. However, the protective effects of OPZ on cerebral I/R injury remain to be elucidated. We investigated the in vitro and in vivo neuroprotective effects of OPZ. Mice were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) to construct an in vivo model and PC12 cells were exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) to establish an in vitro model. OPZ administration reduced the infarct volume and brain water content, and alleviated the neurological deficit of MCAO/R mice. Moreover, OPZ ameliorated MCAO/R-induced oxidative stress by decreasing the levels of 4-HNE and MDA and increasing the activities of SOD and GSH. We also found that OPZ ameliorated MCAO/R-induced ferroptosis by increasing SLC7A11 and GPX4 protein expression and downregulating ACSL4 protein expression. Similarly, the in vitro results revealed that OGD/R-induced oxidative stress and ferroptosis. Finally, mechanistic analysis revealed that OPZ significantly upregulated the Nrf2 expression and Nrf2 knockout (Nrf2 KO) abolished the OPZ-mediated protective effects. Taken together, these findings demonstrate that OPZ ameliorates cerebral I/R injury by suppressing the oxidative stress and ferroptosis.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tionas
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Tiofenos
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Traumatismo por Reperfusão
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Estresse Oxidativo
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Fármacos Neuroprotetores
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Infarto da Artéria Cerebral Média
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Fator 2 Relacionado a NF-E2
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Ferroptose
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Camundongos Endogâmicos C57BL
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China