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Gadolinium Chloride Rescues Niemann–Pick Type C Liver Damage

Niemann–Pick type C (NPC) disease is a rare neurovisceral cholesterol storage disorder that arises from loss of function mutations in the NPC1 or NPC2 genes. Soon after birth, some patients present with an aggressive hepatosplenomegaly and cholestatic signs. Histopathologically, the liver presents w...

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Autores principales: Klein, Andrés D., Oyarzún, Juan Esteban, Cortez, Cristian, Zanlungo, Silvana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274821/
https://www.ncbi.nlm.nih.gov/pubmed/30441844
http://dx.doi.org/10.3390/ijms19113599
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author Klein, Andrés D.
Oyarzún, Juan Esteban
Cortez, Cristian
Zanlungo, Silvana
author_facet Klein, Andrés D.
Oyarzún, Juan Esteban
Cortez, Cristian
Zanlungo, Silvana
author_sort Klein, Andrés D.
collection PubMed
description Niemann–Pick type C (NPC) disease is a rare neurovisceral cholesterol storage disorder that arises from loss of function mutations in the NPC1 or NPC2 genes. Soon after birth, some patients present with an aggressive hepatosplenomegaly and cholestatic signs. Histopathologically, the liver presents with large numbers of foam cells; however, their role in disease pathogenesis has not been explored in depth. Here, we studied the consequences of gadolinium chloride (GdCl(3)) treatment, a well-known Kupffer/foam cell inhibitor, at late stages of NPC liver disease and compared it with NPC1 genetic rescue in hepatocytes in vivo. GdCl(3) treatment successfully blocked the endocytic capacity of hepatic Kupffer/foam measured by India ink endocytosis, decreased the levels CD68—A marker of Kupffer cells in the liver—and normalized the transaminase levels in serum of NPC mice to a similar extent to those obtained by genetic Npc1 rescue of liver cells. Gadolinium salts are widely used as magnetic resonance imaging (MRI) contrasts. This study opens the possibility of targeting foam cells with gadolinium or by other means for improving NPC liver disease. Synopsis: Gadolinium chloride can effectively rescue some parameters of liver dysfunction in NPC mice and its potential use in patients should be carefully evaluated.
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spelling pubmed-62748212018-12-15 Gadolinium Chloride Rescues Niemann–Pick Type C Liver Damage Klein, Andrés D. Oyarzún, Juan Esteban Cortez, Cristian Zanlungo, Silvana Int J Mol Sci Article Niemann–Pick type C (NPC) disease is a rare neurovisceral cholesterol storage disorder that arises from loss of function mutations in the NPC1 or NPC2 genes. Soon after birth, some patients present with an aggressive hepatosplenomegaly and cholestatic signs. Histopathologically, the liver presents with large numbers of foam cells; however, their role in disease pathogenesis has not been explored in depth. Here, we studied the consequences of gadolinium chloride (GdCl(3)) treatment, a well-known Kupffer/foam cell inhibitor, at late stages of NPC liver disease and compared it with NPC1 genetic rescue in hepatocytes in vivo. GdCl(3) treatment successfully blocked the endocytic capacity of hepatic Kupffer/foam measured by India ink endocytosis, decreased the levels CD68—A marker of Kupffer cells in the liver—and normalized the transaminase levels in serum of NPC mice to a similar extent to those obtained by genetic Npc1 rescue of liver cells. Gadolinium salts are widely used as magnetic resonance imaging (MRI) contrasts. This study opens the possibility of targeting foam cells with gadolinium or by other means for improving NPC liver disease. Synopsis: Gadolinium chloride can effectively rescue some parameters of liver dysfunction in NPC mice and its potential use in patients should be carefully evaluated. MDPI 2018-11-14 /pmc/articles/PMC6274821/ /pubmed/30441844 http://dx.doi.org/10.3390/ijms19113599 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Klein, Andrés D.
Oyarzún, Juan Esteban
Cortez, Cristian
Zanlungo, Silvana
Gadolinium Chloride Rescues Niemann–Pick Type C Liver Damage
title Gadolinium Chloride Rescues Niemann–Pick Type C Liver Damage
title_full Gadolinium Chloride Rescues Niemann–Pick Type C Liver Damage
title_fullStr Gadolinium Chloride Rescues Niemann–Pick Type C Liver Damage
title_full_unstemmed Gadolinium Chloride Rescues Niemann–Pick Type C Liver Damage
title_short Gadolinium Chloride Rescues Niemann–Pick Type C Liver Damage
title_sort gadolinium chloride rescues niemann–pick type c liver damage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274821/
https://www.ncbi.nlm.nih.gov/pubmed/30441844
http://dx.doi.org/10.3390/ijms19113599
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