Ghrelin contributes to protection of hepatocellular injury induced by ischaemia/reperfusion

Liver Int. 2014 Apr;34(4):567-75. doi: 10.1111/liv.12286. Epub 2013 Sep 2.

Abstract

Background & aims: Ghrelin, a gut hormone with pleiotropic effects, may act as a protective signal in parenchymal cells. We investigated the protective effects of ghrelin on hepatocytes after ischaemia/reperfusion (I/R).

Methods: Hepatic injury was assessed by measurement of plasma alanine aminotransferase (ALT) and lactate dehydrogenase (LDH), histological analysis, and TUNEL assay. Effects of exogenous ghrelin and ghrelin receptor gene deletion on I/R induced injury of liver were evaluated.

Results: Ischaemia/reperfusion induced a profound injury to hepatocytes. This was accompanied by elevations in plasma ALT and LDH. Pretreatment with ghrelin significantly reduced elevations in plasma ALT and LDH, and attenuated tissue damage induced by hepatic I/R in mice. Hepatic injury induced by I/R was more pronounced in ghrelin receptor gene null mice. Ghrelin administration blocked the up-regulation of AMP-activated protein kinase (AMPK) activity induced by hepatic I/R.

Conclusions: This study demonstrates that ghrelin contributes to the cytoprotection during hepatic I/R.

Keywords: AMPK; Ghrelin; HIRI; ghrelin receptor; gut hormone; liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Alanine Transaminase / blood
  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Gene Deletion
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Ghrelin / pharmacology
  • Ghrelin / therapeutic use*
  • Hepatocytes / drug effects
  • In Situ Nick-End Labeling
  • L-Lactate Dehydrogenase / blood
  • Liver Diseases / etiology*
  • Liver Diseases / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Ghrelin / genetics
  • Reperfusion Injury / complications*

Substances

  • Ghrelin
  • Receptors, Ghrelin
  • L-Lactate Dehydrogenase
  • Alanine Transaminase
  • AMP-Activated Protein Kinases