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

2016: Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death

CBD may represent a novel, protective strategy against I/R injury by attenuating key inflammatory pathways and oxidative/nitrative tissue injury, independent of classical CB1/2 receptors.

Authors:

Mukhopadhyay P, Rajesh M, Horváth B, Bátkai S, Park O, Tanchian G, Gao RY, Patel V, Wink DA, Liaudet L, Haskó G, Mechoulam R, Pacher P.

Abstract:

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 CB2 knockout mice and were not prevented by CB1/2
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 CB1/2
receptors.

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