ArticleBMC pharmacology & toxicology2014
Uridine prevents tamoxifen-induced liver lipid droplet accumulation.
Article in BMC pharmacology & toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- Mass spectrometry imaging reveals spatial metabolic variation and the crucial role of uridine metabolism in liver injury caused by Schistosoma japonicum.PLoS neglected tropical diseases · 2025Article
- Dietary uridine improves lipid homeostasis in high-fat diet-induced obese mice by regulating liver gene expression and metabolomic profiles.Frontiers in nutrition · 2025Article
- Exploring the glucose-lowering and anti-inflammatory immune mechanism of artemether by AMPK/mTOR pathway and microbiome based on multi-omics.Frontiers in pharmacology · 2025Article
- Uridine and its role in metabolic diseases, tumors, and neurodegenerative diseases.Frontiers in physiology · 2024Review
- Effects of the Long-Term Administration of Uridine on the Functioning of Rat Liver Mitochondria in Hyperthyroidism.International journal of molecular sciences · 2023Article
- Confounding Effects of Tamoxifen: Cautionary and Practical Considerations for the Use of Tamoxifen-Inducible Mouse Models in Atherosclerosis Research-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Uridine alleviates high-carbohydrate diet-induced metabolic syndromes by activatingAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2023Article
- Uridine Inhibits Hepatocellular Carcinoma Cell Development by Inducing Ferroptosis.Journal of clinical medicine · 2023Article
- Inhibition ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Effect of Chronic Treatment with Uridine on Cardiac Mitochondrial Dysfunction in the C57BL/6 Mouse Model of High-Fat Diet-Streptozotocin-Induced Diabetes.International journal of molecular sciences · 2022Article
- Renal Metabolome in Obese Mice Treated with Empagliflozin Suggests a Reduction in Cellular Respiration.Biomolecules · 2022Article
- Uncovering the roles of dihydropyrimidine dehydrogenase in fatty-acid induced steatosis using human cellular models.Scientific reports · 2022Article
- Untargeted Metabolomics Reveal Parenteral Nutrition-Associated Alterations in Pediatric Patients with Short Bowel Syndrome.Metabolites · 2022Article
- Tamoxifen induces fatty liver disease in breast cancer through the MAPK8/FoxO pathway.Clinical and translational medicine · 2020Article
- Uridine Metabolism and Its Role in Glucose, Lipid, and Amino Acid Homeostasis.BioMed research international · 2020Review
- Article
- Short-Term Oral UMP/UR Administration Regulates Lipid Metabolism in Early-Weaned Piglets.Animals : an open access journal from MDPI · 2019Article
- Human pyrimidine nucleotide biosynthesis as a target for antiviral chemotherapy.Current opinion in biotechnology · 2017Review
- Drug-induced steatohepatitis.Expert opinion on drug metabolism & toxicology · 2017Review
- Chronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice.PloS one · 2016Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundTamoxifen, an agonist of estrogen receptor, is widely prescribed for the prevention and long-term treatment of breast cancer. A side effect of tamoxifen is fatty liver, which increases the risk for non-alcoholic fatty liver disease. Prevention of tamoxifen-induced fatty liver has the potential to improve the safety of long-term tamoxifen usage.
methodsUridine, a pyrimidine nucleoside with reported protective effects against drug-induced fatty liver, was co-administered with tamoxifen in C57BL/6J mice. Liver lipid levels were evaluated with lipid visualization using coherent anti-Stokes Raman scatting (CARS) microscopy, biochemical assay measurement of triacylglyceride (TAG), and liquid chromatography coupled with mass spectrometry (LC-MS) measurement of membrane phospholipid. Blood TAG and cholesterol levels were measured. Mitochondrial respiration of primary hepatocytes in the presence of tamoxifen and/or uridine was evaluated by measuring oxygen consumption rate with an extracellular flux analyzer. Liver protein lysine acetylation profiles were evaluated with 1D and 2D Western blots. In addition, the relationship between endogenous uridine levels, fatty liver, and tamoxifen administration was evaluated in transgenic mice UPase1-/-and UPase1-TG.
resultsUridine co-administration prevented tamoxifen-induced liver lipid droplet accumulation in mice. The most prominent effect of uridine co-administration with tamoxifen was the stimulation of liver membrane phospholipid biosynthesis. Uridine had no protective effect against tamoxifen-induced impairment to mitochondrial respiration of primary hepatocytes or liver TAG and cholesterol export. Uridine had no effect on tamoxifen-induced changes to liver protein acetylation profile. Transgenic mice UPase1-/-with increased pyrimidine salvage activity were protected against tamoxifen-induced liver lipid droplet accumulation. In contrast, UPase1-TG mice with increased pyrimidine catabolism activity had intrinsic liver lipid droplet accumulation, which was aggravated following tamoxifen administration.
conclusionUridine co-administration was effective at preventing tamoxifen-induced liver lipid droplet accumulation. The ability of uridine to prevent tamoxifen-induced fatty liver appeared to depend on the pyrimidine salvage pathway, which promotes biosynthesis of membrane phospholipid.
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