The Proton Pump Inhibitor Lansoprazole Has Hepatoprotective Effects in In Vitro and In Vivo Rat Models of Acute Liver Injury.

Animals Cells, Cultured Disease Models, Animal Hepatocytes / drug effects Lansoprazole / pharmacology Liver / drug effects Liver Failure, Acute / chemically induced NF-kappa B / metabolism Nitric Oxide / metabolism Nitric Oxide Synthase Type II / metabolism Protective Agents / pharmacology Proton Pump Inhibitors / pharmacology Rats Treatment Outcome Tumor Necrosis Factor-alpha / metabolism
Acute liver injury D-galactosamine with lipopolysaccharide Inducible nitric oxide synthase Lansoprazole Nuclear factor-kappa B Primary cultured hepatocytes

Journal

Digestive diseases and sciences
ISSN: 1573-2568
Titre abrégé: Dig Dis Sci
Pays: United States
ID NLM: 7902782

Informations de publication

Date de publication:
10 2019
Historique:
received: 29 12 2018
accepted: 08 04 2019
pubmed: 17 4 2019
medline: 8 5 2020
entrez: 17 4 2019
Statut: ppublish

Résumé

The proton pump inhibitor lansoprazole (LPZ) is clinically used to reduce gastric acid secretion, but little is known about its possible hepatoprotective effects. This study aimed to investigate the hepatoprotective effects of LPZ and its potential mechanisms using in vitro and in vivo rat models of liver injury. For the in vitro model of liver injury, primary cultured rat hepatocytes were treated with interleukin-1β in the presence or absence of LPZ. The influence of LPZ on inducible nitric oxide synthase (iNOS) induction and nitric oxide (NO) production and on the associated signaling pathways was analyzed. For the in vivo model, rats were treated with D-galactosamine (GalN) and lipopolysaccharide (LPS). The effects of LPZ on survival and proinflammatory mediator expression (including iNOS and tumor necrosis factor-α) in these rats were examined. LPZ inhibited iNOS induction partially through suppression of the nuclear factor-kappa B signaling pathway in hepatocytes, thereby reducing potential liver injury from excessive NO levels. Additionally, LPZ increased survival by 50% and decreased iNOS, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-1 mRNA expression in the livers of GalN/LPS-treated rats. LPZ also inhibited nuclear factor-kappa B activation by GalN/LPS. LPZ inhibits the induction of several inflammatory mediators (including cytokines, chemokines, and NO) partially through suppression of nuclear factor-kappa B, resulting in the prevention of fulminant liver failure. The therapeutic potential of LPZ for liver injuries warrants further investigation.

Sections du résumé

BACKGROUND/AIMS
The proton pump inhibitor lansoprazole (LPZ) is clinically used to reduce gastric acid secretion, but little is known about its possible hepatoprotective effects. This study aimed to investigate the hepatoprotective effects of LPZ and its potential mechanisms using in vitro and in vivo rat models of liver injury.
METHODS
For the in vitro model of liver injury, primary cultured rat hepatocytes were treated with interleukin-1β in the presence or absence of LPZ. The influence of LPZ on inducible nitric oxide synthase (iNOS) induction and nitric oxide (NO) production and on the associated signaling pathways was analyzed. For the in vivo model, rats were treated with D-galactosamine (GalN) and lipopolysaccharide (LPS). The effects of LPZ on survival and proinflammatory mediator expression (including iNOS and tumor necrosis factor-α) in these rats were examined.
RESULTS
LPZ inhibited iNOS induction partially through suppression of the nuclear factor-kappa B signaling pathway in hepatocytes, thereby reducing potential liver injury from excessive NO levels. Additionally, LPZ increased survival by 50% and decreased iNOS, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-1 mRNA expression in the livers of GalN/LPS-treated rats. LPZ also inhibited nuclear factor-kappa B activation by GalN/LPS.
CONCLUSIONS
LPZ inhibits the induction of several inflammatory mediators (including cytokines, chemokines, and NO) partially through suppression of nuclear factor-kappa B, resulting in the prevention of fulminant liver failure. The therapeutic potential of LPZ for liver injuries warrants further investigation.

Identifiants

DOI: 10.1007/s10620-019-05622-6 PMID: 30989463
pubmed: 30989463
doi: 10.1007/s10620-019-05622-6
pii: 10.1007/s10620-019-05622-6
doi:

Substances chimiques

NF-kappa B 0
Protective Agents 0
Proton Pump Inhibitors 0
Tumor Necrosis Factor-alpha 0
Lansoprazole 0K5C5T2QPG
Nitric Oxide 31C4KY9ESH
Nitric Oxide Synthase Type II EC 1.14.13.39

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2854-2866

Références

J Biol Chem. 2000 Feb 11;275(6):4369-73
pubmed: 10660607
Genes Cells. 2000 Feb;5(2):111-25
pubmed: 10672042
Aliment Pharmacol Ther. 2000 Aug;14(8):963-78
pubmed: 10930890
Trends Pharmacol Sci. 2000 Jul;21(7):249-52
pubmed: 10979862
Cancer Lett. 2001 Dec 28;174(2):103-13
pubmed: 11689285
Int J Clin Pract. 2002 Mar;56(2):132-9
pubmed: 11926700
Am J Physiol Gastrointest Liver Physiol. 2002 Aug;283(2):G256-65
pubmed: 12121871
Shock. 2002 Aug;18(2):152-7
pubmed: 12166779
Am J Physiol Cell Physiol. 2003 Aug;285(2):C334-42
pubmed: 12700136
In Vivo. 2003 May-Jun;17(3):293-9
pubmed: 12929583
J Hepatol. 2004 Jan;40(1):94-101
pubmed: 14672619
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2040-5
pubmed: 14764894
J Hepatol. 2004 Apr;40(4):616-23
pubmed: 15030977
Eur J Pharmacol. 2004 Oct 1;500(1-3):255-66
pubmed: 15464038
J Hepatol. 2004 Nov;41(5):730-6
pubmed: 15519644
J Hepatol. 2005 Jan;42(1):94-101
pubmed: 15629513
J Surg Res. 2006 Jan;130(1):88-93
pubmed: 16271365
JPEN J Parenter Enteral Nutr. 2007 Sep-Oct;31(5):373-80; discussion 380-1
pubmed: 17712145
Methods Cell Biol. 1976;13:29-83
pubmed: 177845
Nitric Oxide. 2008 Mar;18(2):105-12
pubmed: 18078833
J Hepatol. 2008 Feb;48(2):289-99
pubmed: 18096265
Shock. 2008 Sep;30(3):311-7
pubmed: 18277953
J Clin Biochem Nutr. 2007 Nov;41(3):154-9
pubmed: 18299709
Mol Nutr Food Res. 2008 Jun;52 Suppl 1:S84-94
pubmed: 18435489
Cell Struct Funct. 1991 Jun;16(3):203-7
pubmed: 1913852
J Toxicol Sci. 2009 Feb;34(1):27-38
pubmed: 19182433
J Pharmacol Sci. 2009 Jul;110(3):285-94
pubmed: 19542683
J Clin Biochem Nutr. 2009 Jul;45(1):86-92
pubmed: 19590712
J Pharmacol Exp Ther. 2009 Oct;331(1):255-64
pubmed: 19628634
Biochim Biophys Acta. 2009 Oct;1790(10):1149-60
pubmed: 19664690
Physiol Genomics. 2009 Nov 6;39(3):227-35
pubmed: 19737990
Shock. 2010 Sep;34 Suppl 1:4-14
pubmed: 20523270
J Physiol Pharmacol. 2010 Jun;61(3):287-94
pubmed: 20610858
PLoS Biol. 2010 Jun 29;8(6):e1000412
pubmed: 20613859
Ann N Y Acad Sci. 2011 Jul;1229:184-9
pubmed: 21793854
Curr Pharm Des. 2013;19(1):67-75
pubmed: 22950496
Hepatol Res. 2014 May;44(5):571-83
pubmed: 23647831
PLoS One. 2013 Jun 11;8(6):e65685
pubmed: 23776526
Anal Biochem. 1987 Apr;162(1):156-9
pubmed: 2440339
PLoS One. 2014 May 20;9(5):e97419
pubmed: 24846271
Trends Pharmacol Sci. 2015 Aug;36(8):524-36
pubmed: 26027855
Inflamm Allergy Drug Targets. 2015;14(2):77-83
pubmed: 27026409
Lab Anim. 2016 Dec;50(6):459-467
pubmed: 27909196
Lab Anim. 2018 Apr;52(2):135-141
pubmed: 28771074
Nat Commun. 2017 Oct 16;8(1):837
pubmed: 29038503
Anal Biochem. 1982 Oct;126(1):131-8
pubmed: 7181105
Annu Rev Cell Biol. 1994;10:405-55
pubmed: 7888182
Am J Respir Cell Mol Biol. 1994 Oct;11(4):464-72
pubmed: 7917314
Prostaglandins. 1993 May;45(5):459-74
pubmed: 8321915
Infect Immun. 1996 Mar;64(3):734-8
pubmed: 8641774
Hepatology. 1996 Apr;23(4):797-802
pubmed: 8666334
Am J Physiol. 1996 Jun;270(6 Pt 1):G956-61
pubmed: 8764202
Hepatology. 1997 Feb;25(2):416-20
pubmed: 9021956
Anal Biochem. 1976 May 7;72:248-54
pubmed: 942051

Auteurs

Richi Nakatake (R)

Department of Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan. nakatakr@hirakata.kmu.ac.jp.
ORCID: 0000-0002-7909-9570

Hidehiko Hishikawa (H)

Department of Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.

Masaya Kotsuka (M)

Department of Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.

Morihiko Ishizaki (M)

Department of Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.

Kosuke Matsui (K)

Department of Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.

Mikio Nishizawa (M)

Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan.

Katsuhiko Yoshizawa (K)

Laboratory of Environmental Sciences, Department of Food Sciences and Nutrition, School of Human Environmental Sciences, Mukogawa Women's University, 6-46 Ikebiraki-cho, Nishinomiya, Hyogo, 663-8558, Japan.

Masaki Kaibori (M)

Department of Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.

Tadayoshi Okumura (T)

Department of Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
Research Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › The Proton Pump Inhibitor Lansoprazole Has...
questionsmedicales.fr › Cellules › Cellules cultivées › The Proton Pump Inhibitor Lansoprazole Has...
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questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Benzimidazoles › (Pyridin-2-ylméthyl)sulfinyl-1H-benzimidazoles › Lansoprazole › The Proton Pump Inhibitor Lansoprazole Has...
questionsmedicales.fr › Système digestif › Foie › The Proton Pump Inhibitor Lansoprazole Has...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Insuffisance hépatique › Défaillance hépatique › Défaillance hépatique aigüe › The Proton Pump Inhibitor Lansoprazole Has...
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questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Agents protecteurs › The Proton Pump Inhibitor Lansoprazole Has...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de la pompe à protons › The Proton Pump Inhibitor Lansoprazole Has...
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