Exacerbated LPS/GalN-Induced Liver Injury in the Stress-Sensitive Wistar Kyoto Rat Is Associated with Changes in the Endocannabinoid System

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dc.citation.issue17
dc.citation.volume25
dc.contributor.authorKillilea M
dc.contributor.authorKerr DM
dc.contributor.authorMallard BM
dc.contributor.authorRoche M
dc.contributor.authorWheatley AM
dc.date.available2020-08-23
dc.date.issued2020-09
dc.description.abstractAcute liver injury (ALI) is a highly destructive and potentially life-threatening condition, exacerbated by physical and psychological stress. The endocannabinoid system plays a key role in modulating stress and hepatic function. The aim of this study was to examine the development of acute liver injury in the genetically susceptible stress-sensitive Wistar-Kyoto (WKY) rat compared with normo-stress-sensitive Sprague Dawley (SD) rats, and associated changes in the endocannabinoid system. Administration of the hepatotoxin lipopolysaccharide/D-Galactosamine (LPS/GalN) resulted in marked liver injury in WKY, but not SD rats, with increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) plasma levels, significant histopathological changes, increased hepatic pro-inflammatory cytokine expression and caspase-3 activity and expression and reduced Glutathione (GSH) activity. Furthermore, compared to SD controls, WKY rats display increased anandamide and 2-Arachidonoylglycerol levels concurrent with decreased expression of their metabolic enzymes and a decrease in cannabinoid (CB)1 receptor expression following LPS/GalN. CB1 antagonism with AM6545 or CB2 agonism with JWH133 did not alter LPS/GalN-induced liver injury in SD or WKY rats. These findings demonstrate exacerbation of acute liver injury induced by LPS/GalN in a stress-sensitive rat strain, with effects associated with alterations in the hepatic endocannabinoid system. Further studies are required to determine if the endocannabinoid system mediates or modulates the exacerbation of liver injury in this stress-sensitive rat strain.
dc.description.confidentialfalse
dc.format.extent3834 - 3834 (16)
dc.identifierhttps://www.mdpi.com/
dc.identifier.citationMolecules, 2020, 25 (17), pp. 3834 - 3834 (16)
dc.identifier.doi10.3390/molecules25173834
dc.identifier.elements-id441001
dc.identifier.harvestedMassey_Dark
dc.identifier.issn1420-3049
dc.publisherMDPI (Basel, Switzerland)
dc.publisher.urihttps://www.mdpi.com/
dc.relation.isPartOfMolecules
dc.relation.replaceshttp://hdl.handle.net/123456789/21736
dc.relation.replaces123456789/21736
dc.relation.urihttps://www.mdpi.com/1420-3049/25/17/3834/htm
dc.subject.anzsrc0304 Medicinal and Biomolecular Chemistry
dc.subject.anzsrc0305 Organic Chemistry
dc.subject.anzsrc0307 Theoretical and Computational Chemistry
dc.titleExacerbated LPS/GalN-Induced Liver Injury in the Stress-Sensitive Wistar Kyoto Rat Is Associated with Changes in the Endocannabinoid System
dc.typeJournal article
pubs.notesNot known
pubs.organisational-group/Massey University
pubs.organisational-group/Massey University/College of Health
pubs.organisational-group/Massey University/College of Health/School of Health Science
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