Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 64Gout, Hyperuricemia, Uric AcidLiver Disease Diagnosis and TreatmentDiet, Metabolism, and Disease

The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.

Hepatic Accumulation of Hypoxanthine: A Link Between Hyperuricemia and Nonalcoholic Fatty Liver Disease

Open access
Toledo-Ibelles, Paola, Gutiérrez-Vidal, Roxana, Calixto-Tlacomulco, Sandra, Delgado-Coello, Blanca, Mas-Oliva, Jaime·2021·Archives of Medical Research
DOI 10.1016/j.arcmed.2021.04.005
Open this paper in CoChat — free accountOpen PDF

Abstract

An elevated level of plasma uric acid has been widely recognized as a risk factor for non-alcoholic fatty liver disease (NAFLD), where oxidative stress and inflammation play an important role in the pathophysiology of the disease. Although the complete molecular mechanisms involved remain unknown, while under physiological conditions uric acid presents antioxidant properties, hyperuricemia has been linked to oxidative stress, chronic low-grade inflammation, and insulin resistance, basic signs of NAFLD. Employing in vivo experimentation, we aim to investigate whether a high-fat diet rich in cholesterol (HFD), modifies the metabolism of purines in close relationship to molecular events associated with the development of NAFLD. In vitro experiments employing HepG2 cells are also carried out to study the phenomenon of oxidative stress. Adult male rabbits were fed for 8 weeks an HFD to induce NAFLD. At the beginning of the experiment and every 15 d until the completion of the study, plasma levels of lipids, lipoproteins, and uric acid were measured. Liver tissue was isolated, and histology performed followed by the biochemical determination of hypoxanthine, protein expression of xanthine oxidoreductase (XOR) by western blot analysis, and xanthine oxidase (XO) activity using an enzymatic kinetic assay. Furthermore, we employed in vitro experimentation studying HepG2 cells to measure the effect of hypoxanthine and H2O2 upon the production of radical oxygen species (ROS), XO activity, and cell viability. Hepatic tissue from rabbits fed the HFD diet showed signs of NAFLD associated with an increased ROS concentration and an altered purine metabolism characterized by the increase in hypoxanthine, together with an apparent equilibrium displacement of XOR towards the xanthine dehydrogenase (XDH) isoform of the enzyme. This protein shift visualized by a western blot analysis, associated with an increase in plasma uric acid and hepatocyte hypoxanthine could be understood as a compensatory series of events secondary to the establishment of oxidative stress associated with the chronic establishment of fatty liver disease.

Overview

Integrity signals

Registry

Crossref · 10.1016/j.arcmed.2021.04.005

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Cited by

See all 64

Metadata

Authors
Toledo-Ibelles, P., Gutiérrez-Vidal, R., Calixto-Tlacomulco, S., Delgado-Coello, B., & Mas-Oliva, J.
Affiliations
Universidad Nacional Autónoma de México (MX)
ORCID
Venue
Archives of Medical Research
Publisher
Elsevier BV
Published
2021-10
Volume
52
Issue
7
Pages
692-702
ISSN
  • 0066-6769 (ISSN-L)
  • 0188-4409
DOI
10.1016/j.arcmed.2021.04.005
OpenAlex
W3159156911
Cited by
64
References
49
Citations by year
2026: 9 · 2025: 20 · 2024: 16 · 2023: 9 · 2022: 8 · 2021: 2
FWCI
5.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Archives of Medical Research (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Universidad Nacional Autónoma de México
  • CONACYT
Topics
  • Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
  • Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
hypoxanthine, hyperuricemia, non-alcoholic fatty liver disease, purine metabolism, xanthine oxidoreductase, xanthine oxidase, xanthine dehydrogenase, oxidative stress, reactive oxygen species, high-fat diet, cholesterol, hepatocyte viability, HepG2 cells, rabbit model
MeSH terms
Animals, Hydrogen Peroxide, Liver, Male, Rabbits, Hypoxanthine, Hyperuricemia, Non-alcoholic Fatty Liver Disease

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.