Short-term therapy with peroxisome proliferation-activator receptor-alpha agonist Wy-14,643 protects murine fatty liver against ischemia-reperfusion injury

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Narci TeohGeoffrey C Farrell

Abstract

Steatosis increases operative morbidity/mortality from ischemia-reperfusion injury (IRI); few pharmacological approaches have been protective. Using novel genetic/dietary models of nonalcoholic steatohepatitis (NASH) and simple steatosis (SS) in Alms1 mutant (foz/foz) mice, we characterized severity of IRI in NASH versus SS and lean liver and tested our hypothesis that the lipid-lowering effects of the peroxisome proliferation-activator receptor (PPAR)-alpha agonist Wy-14,643 would be hepatoprotective. Mice were subjected to 60-minute partial hepatic IRI. Microvascular changes were assessed at 15-minute reperfusion by in vivo microscopy, injury at 24 hours by serum alanine aminotransferase (ALT), and hepatic necrosis area. Injury and inflammation mediators were determined by way of immunoblotting for intercellular cellular adhesion molecule, vascular cellular adhesion molecule, p38, c-jun N-terminal kinase, IkappaB-alpha, interleukin (IL)-1a, IL-12, tumor necrosis factor-alpha (TNF-alpha) and IL-6, cell cycle by cyclin D1 and proliferating cell nuclear antigen immunohistochemistry. In foz/foz mice fed a high-fat diet (HFD) to cause NASH or chow (SS), IRI was exacerbated compared with HFD-fed or chow-fed wild-type littermates by...Continue Reading

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Citations

Feb 23, 2012·Journal of Gastroenterology and Hepatology·Narci C Teoh
Apr 22, 2014·Transplantation Reviews·Sohaib Khalid HashmiAbraham Shaked
Nov 6, 2015·BioMed Research International·Eirini PantaziJoan Roselló-Catafau
Jan 10, 2017·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Pei-Chang LeeShou-Dong Lee
Mar 20, 2015·Liver International : Official Journal of the International Association for the Study of the Liver·Hussam AjamiehNarci C Teoh

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