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Sex-Dependent Hepatomegaly, and Increased Hepatic Oxidative Stress in Old Male and Female 3xTg-AD Mice as Compared to Mice with Physiological Aging †

Juan Fraile-Ramos
1 and
Lydia Giménez-Llort
Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
Author to whom correspondence should be addressed.
Presented at the 2nd International Electronic Conference on Brain Sciences, 15–30 July 2021. Available online:
Med. Sci. Forum 2022, 8(1), 8;
Published: 14 July 2021
(This article belongs to the Proceedings of The 2nd International Electronic Conference on Brain Sciences)


When it comes to neurodegenerative disorders, Alzheimer’s disease (AD) is one of the main causes of dementia in older people. Until now, studies have focused on alterations occurring in the brain. However, it has been shown that along with the accumulation of beta-amyloid plaques and tau proteins, oxidative stress and inflammation also play a role in this disease’s pathophysiology. Peripheral organs such as the liver, the central organ regulating metabolism and supporting the immune system, could affect AD pathophysiological development and/or progress. We have previously described hepatic oxidative stress in 6-month-old 3xTg-AD mice, an age mimicking the prodromal stages of AD disease. In the present work, we studied the impact of AD-genotype and sex effects on liver dysfunction in 16-month-old male and female 3xTg-AD mice, an age mimicking advanced neuropathological stages of the disease, and as compared to age- and sex-matched non-transgenic mice with physiological aging. The mass index results showed hepatic damage as hepatomegaly in 3xTg-AD mice. A sex-dependent increase in hepatic tissue oxidative stress, measured through antioxidant enzymes glutathione reductase (Gr) and glutathione peroxidase (Gpx), and antioxidant compound glutathione (GSH), was found in 3xTg-AD mice. Furthermore, the correlations between the enzymes and the hepatic index also showed sex and genotype differences. These results indicate that liver status is affected in 3xTg-AD mice; it is affected in a sexually differential manner and could favor AD progression. Further ongoing analysis regarding β-amyloid and lipidic depositions on the liver would determine if these alterations correlate with a worse prognosis of the disease.

Supplementary Materials

The following supporting information can be downloaded at: References [1,2,3,4,5,6,7,8] are cited in the Supplementary Materials.

Author Contributions

L.G.-L.: conceptualization and supervision; J.F.-R.: writing and formal analysis. Both authors revised and approved the final manuscript. All authors have read and agreed to the published version of the manuscript.


The colonies are currently sustained by Fet-Open ArrestAD European Union’s Horizon 2020 research and innovation program under grant agreement No. 737390 to L.G.-L.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Departament de Medi Ambient i Habitatge, Generalitat de Catalunya (CEEAH 3588/DMAH 9452) on 8 March 2019.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data are not publicly available due to ongoing analyses for future publications.


We thank Frank M. LaFerla, from the Institute for Memory Impairments and Neurological Disorders, Department of Neurobiology and Behavior, University of California, Irvine, USA, for kindly providing the progenitors of the Spanish colonies of 3xTg-AD and NTg mice.

Conflicts of Interest

The authors declare no conflict of interest.


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MDPI and ACS Style

Fraile-Ramos, J.; Giménez-Llort, L. Sex-Dependent Hepatomegaly, and Increased Hepatic Oxidative Stress in Old Male and Female 3xTg-AD Mice as Compared to Mice with Physiological Aging. Med. Sci. Forum 2022, 8, 8.

AMA Style

Fraile-Ramos J, Giménez-Llort L. Sex-Dependent Hepatomegaly, and Increased Hepatic Oxidative Stress in Old Male and Female 3xTg-AD Mice as Compared to Mice with Physiological Aging. Medical Sciences Forum. 2022; 8(1):8.

Chicago/Turabian Style

Fraile-Ramos, Juan, and Lydia Giménez-Llort. 2022. "Sex-Dependent Hepatomegaly, and Increased Hepatic Oxidative Stress in Old Male and Female 3xTg-AD Mice as Compared to Mice with Physiological Aging" Medical Sciences Forum 8, no. 1: 8.

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