Ghrelin reduces liver impairment in a model of concanavalin A-induced acute hepatitis in mice

Content Provider	Semantic Scholar
Author	Mao, Yuqing Wang, Jianbo Yu, Fujun Cheng, Jian Li, Huanqing Guo, Chuanyong Fan, Xiaoming
Copyright Year	2015
Abstract	BACKGROUND AND AIMS Ghrelin is a 28-amino-acid gut hormone that was first discovered as a potent growth hormone secretagogue. Recently, it has been shown to exert a strong anti-inflammatory effect. The purpose of the study reported here was to explore the effect and mechanism of ghrelin on concanavalin (Con) A-induced acute hepatitis. METHODS Balb/C mice were divided into four groups: normal control (NC) (mice injected with vehicle [saline]); Con A (25 mg/kg); Con A + 10 μg/kg ghrelin; and Con A + 50 μg/kg ghrelin (1 hour before Con A injection). Pro-inflammatory cytokine levels were detected. Protein levels of phosphoinositide 3-kinase (PI3K); phosphorylated Akt (p-Akt); caspase 3, 8, and 9; and microtubule-associated protein 1 light chain 3 (LC3) were also detected. Perifosine (25 mM) (an Akt inhibitor) was used to investigate whether the protective effect of ghrelin was interrupted by an Akt inhibitor. Protein levels of p-AKT; Bcl-2; Bax; and caspase 3, 8, and 9 were also detected. RESULTS Aspartate aminotransferase, alanine aminotransferase, and pathological damage were significantly ameliorated by ghrelin pretreatment in Con A-induced hepatitis. Inflammatory cytokines were significantly reduced by ghrelin pretreatment. Bcl-2; Bax; and caspase 3, 8, and 9 expression were also clearly affected by ghrelin pretreatment, compared with the Con A-treated group. However, the Akt kinase inhibitor reversed the decrease of Bax and caspase 3, 8, 9, and reduced the protein level of p-Akt and Bcl-2. Ghrelin activated the PI3K/Akt/Bcl-2 pathway and inhibited activation of autophagy. CONCLUSION Our results demonstrate that ghrelin attenuates Con A-induced acute immune hepatitis by activating the PI3K/Akt pathway and inhibiting the process of autophagy, which might be related to inhibition of inflammatory cytokine release, and prevention of hepatocyte apoptosis. These effects could be interrupted by an Akt kinase inhibitor.
Starting Page	5385
Ending Page	5396
Page Count	12
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://www.dovepress.com/getfile.php?fileID=27247
Alternate Webpage(s)	https://pdfs.semanticscholar.org/d1f6/d51d4a6566b950f8754ca60cc25652919df8.pdf
PubMed reference number	26451091v1
Alternate Webpage(s)	https://doi.org/10.2147/DDDT.S89096
DOI	10.2147/dddt.s89096
Journal	Drug design, development and therapy
Volume Number	9
Language	English
Access Restriction	Open
Subject Keyword	1-Phosphatidylinositol 3-Kinase 1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase Acute hepatitis Alanine Transaminase Apoptosis Appetite-Regulating Hormone Aspartate Transaminase Aspartic Acid Autophagy BCL2 gene Chemical and Drug Induced Liver Injury Concanavalin A Inhibition Liver diseases Microtubule-Associated Proteins 1A/1B Light Chain 3 Microtubules Phosphatidylinositols Proto-Oncogene Proteins c-akt Transaminases caspase-3 cytokine ghrelin hepatocyte apoptotic process mg/kg perifosine
Content Type	Text
Resource Type	Article