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Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death.
Free Radic Biol Med 2011; 50(10):1368-81FR

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.

Authors+Show Affiliations

Laboratory of Physiologic Studies, National Institutes of Health, Bethesda, MD 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21362471

Citation

Mukhopadhyay, Partha, et al. "Cannabidiol Protects Against Hepatic Ischemia/reperfusion Injury By Attenuating Inflammatory Signaling and Response, Oxidative/nitrative Stress, and Cell Death." Free Radical Biology & Medicine, vol. 50, no. 10, 2011, pp. 1368-81.
Mukhopadhyay P, Rajesh M, Horváth B, et al. Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death. Free Radic Biol Med. 2011;50(10):1368-81.
Mukhopadhyay, P., Rajesh, M., Horváth, B., Bátkai, S., Park, O., Tanchian, G., ... Pacher, P. (2011). Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death. Free Radical Biology & Medicine, 50(10), pp. 1368-81. doi:10.1016/j.freeradbiomed.2011.02.021.
Mukhopadhyay P, et al. Cannabidiol Protects Against Hepatic Ischemia/reperfusion Injury By Attenuating Inflammatory Signaling and Response, Oxidative/nitrative Stress, and Cell Death. Free Radic Biol Med. 2011 May 15;50(10):1368-81. PubMed PMID: 21362471.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death. AU - Mukhopadhyay,Partha, AU - Rajesh,Mohanraj, AU - Horváth,Béla, AU - Bátkai,Sándor, AU - Park,Ogyi, AU - Tanchian,Galin, AU - Gao,Rachel Y, AU - Patel,Vivek, AU - Wink,David A, AU - Liaudet,Lucas, AU - Haskó,György, AU - Mechoulam,Raphael, AU - Pacher,Pál, Y1 - 2011/03/11/ PY - 2010/10/26/received PY - 2011/02/07/revised PY - 2011/02/19/accepted PY - 2011/3/3/entrez PY - 2011/3/3/pubmed PY - 2011/9/14/medline SP - 1368 EP - 81 JF - Free radical biology & medicine JO - Free Radic. Biol. Med. VL - 50 IS - 10 N2 - 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. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/21362471/Cannabidiol_protects_against_hepatic_ischemia/reperfusion_injury_by_attenuating_inflammatory_signaling_and_response_oxidative/nitrative_stress_and_cell_death_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(11)00126-2 DB - PRIME DP - Unbound Medicine ER -