Next Article in Journal
Ethinylestradiol and Levonorgestrel as Active Agents in Normal Skin, and Pathological Conditions Induced by UVB Exposure: In Vitro and In Ovo Assessments
Next Article in Special Issue
Mutations in the GLA Gene and LysoGb3: Is It Really Anderson-Fabry Disease?
Previous Article in Journal
Emerging Role of Purine Metabolizing Enzymes in Brain Function and Tumors
Previous Article in Special Issue
Main Olfactory and Vomeronasal Epithelium Are Differently Affected in Niemann-Pick Disease Type C1
Article Menu
Issue 11 (November) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(11), 3599; https://doi.org/10.3390/ijms19113599

Gadolinium Chloride Rescues Niemann–Pick Type C Liver Damage

1
Centro de Genética y Genómica, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago 7590943, Chile
2
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile
3
Center for Genomic and Bioinformatic, Faculty of Sciences, Universidad Mayor, Santiago 8580745, Chile
*
Authors to whom correspondence should be addressed.
Received: 29 September 2018 / Revised: 1 November 2018 / Accepted: 2 November 2018 / Published: 14 November 2018
(This article belongs to the Special Issue Molecular Features of Lysosomal Storage Disorders)
Full-Text   |   PDF [2926 KB, uploaded 14 November 2018]   |  

Abstract

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 (GdCl3) 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. GdCl3 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. View Full-Text
Keywords: Niemann–Pick type C disease; gadolinium chloride; liver disease; cholesterol; therapeutic option Niemann–Pick type C disease; gadolinium chloride; liver disease; cholesterol; therapeutic option
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Klein, A.D.; Oyarzún, J.E.; Cortez, C.; Zanlungo, S. Gadolinium Chloride Rescues Niemann–Pick Type C Liver Damage. Int. J. Mol. Sci. 2018, 19, 3599.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top