Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death.

Détails

Ressource 1Télécharger: BIB_F1F3C7827701.P001.pdf (4371.71 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_F1F3C7827701
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death.
Périodique
Free Radical Biology and Medicine
Auteur(s)
Mukhopadhyay P., Rajesh M., Horváth B., Bátkai S., Park O., Tanchian G., Gao R.Y., Patel V., Wink D.A., Liaudet L., Haskó G., Mechoulam R., Pacher P.
ISSN
1873-4596 (Electronic)
ISSN-L
0891-5849
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
50
Numéro
10
Pages
1368-1381
Langue
anglais
Résumé
Ischemia/reperfusion (I/R) is a pivotal mechanism of liver damage after liver transplantation or hepatic surgery. We have investigated the effects of cannabidiol (CBD), the nonpsychotropic constituent of marijuana, in a mouse model of hepatic I/R injury. I/R triggered time-dependent increases/changes in markers of liver injury (serum transaminases), hepatic oxidative/nitrative stress (4-hydroxy-2-nonenal, nitrotyrosine content/staining, and gp91phox and inducible nitric oxide synthase mRNA), mitochondrial dysfunction (decreased complex I activity), inflammation (tumor necrosis factor α (TNF-α), cyclooxygenase 2, macrophage inflammatory protein-1α/2, intercellular adhesion molecule 1 mRNA levels; tissue neutrophil infiltration; nuclear factor κB (NF-κB) activation), stress signaling (p38MAPK and JNK), and cell death (DNA fragmentation, PARP activity, and TUNEL). CBD significantly reduced the extent of liver inflammation, oxidative/nitrative stress, and cell death and also attenuated the bacterial endotoxin-triggered NF-κB activation and TNF-α production in isolated Kupffer cells, likewise the adhesion molecule expression in primary human liver sinusoidal endothelial cells stimulated with TNF-α and attachment of human neutrophils to the activated endothelium. These protective effects were preserved in CB(2) knockout mice and were not prevented by CB(1/2) antagonists in vitro. Thus, CBD may represent a novel, protective strategy against I/R injury by attenuating key inflammatory pathways and oxidative/nitrative tissue injury, independent of classical CB(1/2) receptors.
Pubmed
Web of science
Création de la notice
08/06/2011 10:45
Dernière modification de la notice
03/03/2018 22:39
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