Endozepine-4 levels are increased in hepatic coma

doi:10.3748/wjg.v21.i30.9103

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World Journal of Gastroenterology

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World J Gastroenterol. Aug 14, 2015; 21(30): 9103-9110
Published online Aug 14, 2015. doi: 10.3748/wjg.v21.i30.9103

Endozepine-4 levels are increased in hepatic coma

Giulia Malaguarnera, Marco Vacante, Filippo Drago, Gaetano Bertino, Massimo Motta, Maria Giordano, Michele Malaguarnera

Giulia Malaguarnera, Marco Vacante, Maria Giordano, Michele Malaguarnera, Research Center “The Great Senescence” Hospital of Cannizzaro, University of Catania, via Messina 829, 95100 Acicastello, Italy

Giulia Malaguarnera, Marco Vacante, Gaetano Bertino, Massimo Motta, Michele Malaguarnera, Department of Clinical and Experimental Medicine, University of Catania, 95125 Catania, Italy

Giulia Malaguarnera, Filippo Drago, Michele Malaguarnera, Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, School of Medicine, University of Catania, 95125 Catania, Italy

Maria Giordano, Gerontology and Bone Metabolic Disease Section, Department of Medical Sciences, University of Torino, 10124 Torino, Italy

Author contributions: Malaguarnera G and Malaguarnera M contributed to the design of the study, biochemical analysis, experimental procedure, interpretation of the data and wrote the manuscript; Vacante M and Giordano M contributed to the statistical analysis and interpretation of the data; Vacante M, Giordano M and Bertino G enrolled the patients; Drago F, Motta M, Bertino G and Malaguarnera M revised the manuscript and coordinated the study.

Institutional review board statement: The study was reviewed and approved by the Hospital Cannizzaro of Catania Institutional Review Board.

Informed consent statement: All the legal guardian of study participants, provided informed written consent prior to study enrollment.

Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.

Data sharing statement: No additional data are available.

Correspondence to: Giulia Malaguarnera, PhD, Research Center “The Great Senescence” Hospital of Cannizzaro, University of Catania, via Messina 829, 95100 Acicastello, Italy. giulia.malaguarnera@live.it

Telephone: +39-095-7262008

Received: December 21, 2014
Peer-review started: December 22, 2014
First decision: February 10, 2015
Revised: March 11, 2015
Accepted: May 7, 2015
Article in press: May 7, 2015
Published online: August 14, 2015
Processing time: 238 Days and 15.7 Hours

Abstract

AIM: To evaluate the serum levels of endozepine-4, their relation with ammonia serum levels, the grading of coma and the severity of cirrhosis, in patients with hepatic coma.

METHODS: In this study we included 20 subjects with Hepatic coma, 20 subjects with minimal hepatic encephalopathy (MHE) and 20 subjects control. All subjects underwent blood analysis, Child Pugh and Model for End - stage liver disease (MELD) assessment, endozepine-4 analysis.

RESULTS: Subjects with hepatic coma showed significant difference in endozepine-4 (P < 0.001) and NH3 levels (P < 0.001) compared both to MHE and controls patients. Between NH₃ and endozepine-4 we observed a significant correlation (P = 0.009; Pearson correlation 0.570). There was a significant correlation between endozepine-4 and MELD (P = 0.017; Pearson correlation = 0.529). In our study blood ammonia concentration was noted to be raised in patients with hepatic coma, with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia (P < 0.001). In patients with grade IV hepatic coma, endozepine levels were significantly higher compared to other groups.

CONCLUSION: This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion, data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations.

Keywords: Endozepine-4; Hepatic encephalopathy; Hepatic coma; Cirrhosis, Benzodiazepine; Peripheral benzodiazepine receptor; Model for End - stage liver disease; Glutamate-related neurotoxicity which in turn may alter the γ-aminobutyric acid

Core tip: Endozepine-4 is an endogenous ligand for the benzodiazepine recognition site of the glutamate-related neurotoxicity which in turn may alter the γ-aminobutyric acid (GABA)_A receptor. Endozepine-4, may play an important role in the pathogenesis of hepatic encephalopathy (HE). The pathogenesis of HE has been viewed as a multifactorial etiology, but ammonia has a pivotal role in the genesis of the disease. Ammonia exerts a GABA_A receptor system Involvement of the GABA-ergic system in HE coma could be due to stage-specific alterations.