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Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion

We aimed to evaluate the magnesium content in human cirrhotic liver and its correlation with serum AST levels, expression of hepatocellular injury, and MELDNa prognostic score. In liver biopsies obtained at liver transplantation, we measured the magnesium content in liver tissue in 27 cirrhotic pati...

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Autores principales: Parisse, Simona, Gianoncelli, Alessandra, Isani, Gloria, Gambaro, Francesco Luigi, Andreani, Giulia, Malucelli, Emil, Aquilanti, Giuliana, Carlomagno, Ilaria, Carletti, Raffaella, Mischitelli, Monica, Ferri, Flaminia, Paterna, Veronica, Lai, Quirino, Mennini, Gianluca, Melandro, Fabio, Di Gioia, Cira, Rossi, Massimo, Iotti, Stefano, Fratini, Michela, Ginanni Corradini, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10255194/
https://www.ncbi.nlm.nih.gov/pubmed/37299589
http://dx.doi.org/10.3390/nu15112626
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author Parisse, Simona
Gianoncelli, Alessandra
Isani, Gloria
Gambaro, Francesco Luigi
Andreani, Giulia
Malucelli, Emil
Aquilanti, Giuliana
Carlomagno, Ilaria
Carletti, Raffaella
Mischitelli, Monica
Ferri, Flaminia
Paterna, Veronica
Lai, Quirino
Mennini, Gianluca
Melandro, Fabio
Di Gioia, Cira
Rossi, Massimo
Iotti, Stefano
Fratini, Michela
Ginanni Corradini, Stefano
author_facet Parisse, Simona
Gianoncelli, Alessandra
Isani, Gloria
Gambaro, Francesco Luigi
Andreani, Giulia
Malucelli, Emil
Aquilanti, Giuliana
Carlomagno, Ilaria
Carletti, Raffaella
Mischitelli, Monica
Ferri, Flaminia
Paterna, Veronica
Lai, Quirino
Mennini, Gianluca
Melandro, Fabio
Di Gioia, Cira
Rossi, Massimo
Iotti, Stefano
Fratini, Michela
Ginanni Corradini, Stefano
author_sort Parisse, Simona
collection PubMed
description We aimed to evaluate the magnesium content in human cirrhotic liver and its correlation with serum AST levels, expression of hepatocellular injury, and MELDNa prognostic score. In liver biopsies obtained at liver transplantation, we measured the magnesium content in liver tissue in 27 cirrhotic patients (CIRs) and 16 deceased donors with healthy liver (CTRLs) by atomic absorption spectrometry and within hepatocytes of 15 CIRs using synchrotron-based X-ray fluorescence microscopy. In 31 CIRs and 10 CTRLs, we evaluated the immunohistochemical expression in hepatocytes of the transient receptor potential melastatin 7 (TRPM7), a magnesium influx chanzyme also involved in inflammation. CIRs showed a lower hepatic magnesium content (117.2 (IQR 110.5–132.9) vs. 162.8 (IQR 155.9–169.8) μg/g; p < 0.001) and a higher percentage of TRPM7 positive hepatocytes (53.0 (IQR 36.8–62.0) vs. 20.7 (10.7–32.8)%; p < 0.001) than CTRLs. In CIRs, MELDNa and serum AST at transplant correlated: (a) inversely with the magnesium content both in liver tissue and hepatocytes; and (b) directly with the percentage of hepatocytes stained intensely for TRPM7. The latter also directly correlated with the worsening of MELDNa at transplant compared to waitlisting. Magnesium depletion and overexpression of its influx chanzyme TRPM7 in hepatocytes are associated with severity of hepatocyte injury and prognosis in cirrhosis. These data represent the pathophysiological basis for a possible beneficial effect of magnesium supplementation in cirrhotic patients.
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spelling pubmed-102551942023-06-10 Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion Parisse, Simona Gianoncelli, Alessandra Isani, Gloria Gambaro, Francesco Luigi Andreani, Giulia Malucelli, Emil Aquilanti, Giuliana Carlomagno, Ilaria Carletti, Raffaella Mischitelli, Monica Ferri, Flaminia Paterna, Veronica Lai, Quirino Mennini, Gianluca Melandro, Fabio Di Gioia, Cira Rossi, Massimo Iotti, Stefano Fratini, Michela Ginanni Corradini, Stefano Nutrients Article We aimed to evaluate the magnesium content in human cirrhotic liver and its correlation with serum AST levels, expression of hepatocellular injury, and MELDNa prognostic score. In liver biopsies obtained at liver transplantation, we measured the magnesium content in liver tissue in 27 cirrhotic patients (CIRs) and 16 deceased donors with healthy liver (CTRLs) by atomic absorption spectrometry and within hepatocytes of 15 CIRs using synchrotron-based X-ray fluorescence microscopy. In 31 CIRs and 10 CTRLs, we evaluated the immunohistochemical expression in hepatocytes of the transient receptor potential melastatin 7 (TRPM7), a magnesium influx chanzyme also involved in inflammation. CIRs showed a lower hepatic magnesium content (117.2 (IQR 110.5–132.9) vs. 162.8 (IQR 155.9–169.8) μg/g; p < 0.001) and a higher percentage of TRPM7 positive hepatocytes (53.0 (IQR 36.8–62.0) vs. 20.7 (10.7–32.8)%; p < 0.001) than CTRLs. In CIRs, MELDNa and serum AST at transplant correlated: (a) inversely with the magnesium content both in liver tissue and hepatocytes; and (b) directly with the percentage of hepatocytes stained intensely for TRPM7. The latter also directly correlated with the worsening of MELDNa at transplant compared to waitlisting. Magnesium depletion and overexpression of its influx chanzyme TRPM7 in hepatocytes are associated with severity of hepatocyte injury and prognosis in cirrhosis. These data represent the pathophysiological basis for a possible beneficial effect of magnesium supplementation in cirrhotic patients. MDPI 2023-06-03 /pmc/articles/PMC10255194/ /pubmed/37299589 http://dx.doi.org/10.3390/nu15112626 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Parisse, Simona
Gianoncelli, Alessandra
Isani, Gloria
Gambaro, Francesco Luigi
Andreani, Giulia
Malucelli, Emil
Aquilanti, Giuliana
Carlomagno, Ilaria
Carletti, Raffaella
Mischitelli, Monica
Ferri, Flaminia
Paterna, Veronica
Lai, Quirino
Mennini, Gianluca
Melandro, Fabio
Di Gioia, Cira
Rossi, Massimo
Iotti, Stefano
Fratini, Michela
Ginanni Corradini, Stefano
Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion
title Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion
title_full Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion
title_fullStr Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion
title_full_unstemmed Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion
title_short Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion
title_sort severity of hepatocyte damage and prognosis in cirrhotic patients correlate with hepatocyte magnesium depletion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10255194/
https://www.ncbi.nlm.nih.gov/pubmed/37299589
http://dx.doi.org/10.3390/nu15112626
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