Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Aging Exacerbates Oxidative Stress and Liver Fibrosis in an Ani-Mal Model of Down Syndrome

Sebastiano Giallongo
,
Veronika Talianova
,
Emanuela Tropea
,
Jessica Ferrigno
,
Rosario Caltabiano
ORCID logo ,
Giuseppe Broggi
ORCID logo ,
Alfio Distefano
,
Amer Alanazi
,
Antonella Tramutola
ORCID logo ,
Marzia Perluigi
,
Eugenio Barone
ORCID logo ,
Ignazio Barbagallo
* ORCID logo
Version 1 : Received: 31 August 2023 / Approved: 1 September 2023 / Online: 4 September 2023 (03:50:26 CEST)

How to cite: Giallongo, S.; Talianova, V.; Tropea, E.; Ferrigno, J.; Caltabiano, R.; Broggi, G.; Distefano, A.; Alanazi, A.; Tramutola, A.; Perluigi, M.; Barone, E.; Barbagallo, I. Aging Exacerbates Oxidative Stress and Liver Fibrosis in an Ani-Mal Model of Down Syndrome. Preprints 2023, 2023090105. https://doi.org/10.20944/preprints202309.0105.v1 Giallongo, S.; Talianova, V.; Tropea, E.; Ferrigno, J.; Caltabiano, R.; Broggi, G.; Distefano, A.; Alanazi, A.; Tramutola, A.; Perluigi, M.; Barone, E.; Barbagallo, I. Aging Exacerbates Oxidative Stress and Liver Fibrosis in an Ani-Mal Model of Down Syndrome. Preprints 2023, 2023090105. https://doi.org/10.20944/preprints202309.0105.v1

Abstract

Abstract: Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and the onset of dementia re-sembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). The liver in DS mice shows increased oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Furthermore, DS liver exhibits an altered in-flammatory response as measured by the expression of cytokines and heat shock proteins. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of peroxisome prolif-erator-activated receptors and fatty acid transport proteins. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Finally, histological analysis of DS liver reveals increased fibrosis and steatosis, in-dicative of potential progression to liver cirrhosis. This finding highlights the increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.

Keywords

down syndrome; oxidative stress; liver; aging

Subject

Medicine and Pharmacology, Endocrinology and Metabolism

Copyright: 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.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.