Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury
Background/Aims: Ischemia/reperfusion (I/R) injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts. Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury. Delta-9-tetrahydrocannabinol (THC), a cannabinoid ag...
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Cell Physiol Biochem Press GmbH & Co KG
2015-07-01
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doaj-dfe6d68bc30a4b1daf9b0ce899f4352b2020-11-25T01:37:49ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-07-013651971198110.1159/000430165430165Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion InjuryEdith HochhauserEylon LahatMaya SultanOrit PappoMaayan WaldmanYosef SarneAsher ShainbergMordechai GutmanMichal SafranZiv Ben AriBackground/Aims: Ischemia/reperfusion (I/R) injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts. Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury. Delta-9-tetrahydrocannabinol (THC), a cannabinoid agonist, is the active components of marijuana. In this study we examined the role of ultralow dose THC (0.002mg/kg) in the protection of livers from I/R injury. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults. Methods: C57Bl Mice were studied in in vivo model of hepatic segmental (70%) ischemia for 60min followed by reperfusion for 6 hours. Results: THC administration 2h prior to the induction of hepatic I/R was associated with significant attenuated elevations of: serum liver transaminases ALT and AST, the hepatic oxidative stress (activation of the intracellular signaling CREB pathway), the acute proinflammatory response (TNF-α, IL-1α, IL-10 and c-FOS hepatic mRNA levels, and ERK signaling pathway activation). This was followed by cell death (the cleavage of the pro-apoptotic caspase 3, DNA fragmentation and TUNEL) after 6 hours of reperfusion. Significantly less hepatic injury was detected in the THC treated I/R mice and fewer apoptotic hepatocytes cells were identified by morphological criteria compared with untreated mice. Conclusion: A single ultralow dose THC can reduce the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury. THC may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation, liver resection and trauma.http://www.karger.com/Article/FullText/430165LiverIschemia/reperfusionDelta 9-tetrahydrocannabinolUltralow dose |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Edith Hochhauser Eylon Lahat Maya Sultan Orit Pappo Maayan Waldman Yosef Sarne Asher Shainberg Mordechai Gutman Michal Safran Ziv Ben Ari |
spellingShingle |
Edith Hochhauser Eylon Lahat Maya Sultan Orit Pappo Maayan Waldman Yosef Sarne Asher Shainberg Mordechai Gutman Michal Safran Ziv Ben Ari Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury Cellular Physiology and Biochemistry Liver Ischemia/reperfusion Delta 9-tetrahydrocannabinol Ultralow dose |
author_facet |
Edith Hochhauser Eylon Lahat Maya Sultan Orit Pappo Maayan Waldman Yosef Sarne Asher Shainberg Mordechai Gutman Michal Safran Ziv Ben Ari |
author_sort |
Edith Hochhauser |
title |
Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury |
title_short |
Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury |
title_full |
Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury |
title_fullStr |
Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury |
title_full_unstemmed |
Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury |
title_sort |
ultra low dose delta 9-tetrahydrocannabinol protects mouse liver from ischemia reperfusion injury |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2015-07-01 |
description |
Background/Aims: Ischemia/reperfusion (I/R) injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts. Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury. Delta-9-tetrahydrocannabinol (THC), a cannabinoid agonist, is the active components of marijuana. In this study we examined the role of ultralow dose THC (0.002mg/kg) in the protection of livers from I/R injury. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults. Methods: C57Bl Mice were studied in in vivo model of hepatic segmental (70%) ischemia for 60min followed by reperfusion for 6 hours. Results: THC administration 2h prior to the induction of hepatic I/R was associated with significant attenuated elevations of: serum liver transaminases ALT and AST, the hepatic oxidative stress (activation of the intracellular signaling CREB pathway), the acute proinflammatory response (TNF-α, IL-1α, IL-10 and c-FOS hepatic mRNA levels, and ERK signaling pathway activation). This was followed by cell death (the cleavage of the pro-apoptotic caspase 3, DNA fragmentation and TUNEL) after 6 hours of reperfusion. Significantly less hepatic injury was detected in the THC treated I/R mice and fewer apoptotic hepatocytes cells were identified by morphological criteria compared with untreated mice. Conclusion: A single ultralow dose THC can reduce the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury. THC may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation, liver resection and trauma. |
topic |
Liver Ischemia/reperfusion Delta 9-tetrahydrocannabinol Ultralow dose |
url |
http://www.karger.com/Article/FullText/430165 |
work_keys_str_mv |
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