Pyrroloquinoline quinone protects against murine hepatitis virus strain 3-induced fulminant hepatitis by inhibiting the Keap1/Nrf2 signaling.
Cytotechnology
; 76(4): 441-452, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38933874
ABSTRACT
Fulminant hepatitis (FH) is a life-threatening clinical liver syndrome characterized by substantial hepatocyte necrosis and severe liver damage. FH is typically associated with severe oxidative stress, inflammation, and mitochondrial dysfunction. Pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor, functions as an essential nutrient and antioxidant and reportedly inhibits oxidative stress and exerts potent anti-inflammatory effects. In the present study, we aimed to evaluate the therapeutic efficacy of PQQ in murine hepatitis virus strain 3 (MHV-3)-induced FH and examined the underlying mechanism. An MHV-3-induced FH mouse model was established for in vivo examination. Liver sinusoidal endothelial cells (LSECs) were used for in vitro experiments. Herein, we observed that PQQ supplementation significantly attenuated MHV-3-induced hepatic injury by suppressing inflammatory responses and reducing oxidative stress. Mechanistically, PQQ supplementation ameliorated MHV-3-induced hepatic damage by down-regulating the Keap1/Nrf2 signaling pathway in vivo and in vitro. Furthermore, Nrf2 small interfering RNA targeting LSECs abrogated the PQQ-mediated protective effects against MHV-3-related liver injury. Our results deepen our understanding of the hepatoprotective function of PQQ against MHV-3-induced liver injury and provide evidence that alleviating oxidative stress might afford a novel therapeutic strategy for treating FH.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cytotechnology
Assunto da revista:
BIOTECNOLOGIA
/
GENETICA
Ano de publicação:
2024
Tipo de documento:
Article