Modulation of Cuproptosis Pathway Genes (DLAT, FDX1) and Antioxidant Enzyme Activities in Obese Mice in Response to Quercetin and Calorie Restriction
- 1 July 2025
- journal article
- Published by SAGE Publications in DNA and Cell Biology
- Vol. 44 (7) , 370-379
Abstract
Cuproptosis is a new mode of cell death that is closely related to mitochondrial stress. The purpose of this study is to investigate the amount of copper, copper-associated genes DLAT and FDX1 oxidative stress (OS) status in obesity. Since there is a close relationship between OS and cuproptosis, evaluating the effect of various strategies to reduce OS, including quercetin (QUER) and caloric restriction (CR), is another goal of this study. In this study, 30 male BALB-C mice aged 8 weeks and weighing 25 g, including the groups receiving normal diet (ND), ND with QUER (15 mg/kg, IP) and CR, a high-fat diet (HFD) with the QUER, CR or a combination of both were used. The activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione reductase (GR), amount of copper in the liver and kidney tissues, and expression of DLAT and FDX1 genes were measured in all studied groups. The amount of copper in the liver and kidney tissue as well as the expression of FDX1 and DLAT in the HFD group increased significantly compared with the ND group. QUER, CR or their combination could significantly reduce the amount of copper as well as the expression of FDX1 and DLAT in liver and kidney tissues. QUER and CR, also significantly increased the activity of GR, SOD and GPX in serum, liver, and kidney tissues. Based on the results, QUER, CR and especially the simultaneous use of both, was able to reduce the amount of copper and its related cuproptosis. These effects may reduce cuproptosis-associated cell death. Therefore, the use of antioxidants and CR may be a promising solution to protect the human body against the effects of cuproptosis in conditions like obesity.Keywords
This publication has 49 references indexed in Scilit:
- Quercetin Attenuates Acute Kidney Injury Caused by Cisplatin by Inhibiting Ferroptosis and CuproptosisCell Biochemistry and Biophysics, 2024
- Cuproptosis: Mechanism, role, and advances in urological malignanciesMedicinal Research Reviews, 2024
- Ferroptosis and cuproptposis in kidney Diseases: dysfunction of cell metabolismApoptosis, 2023
- The molecular mechanisms of cuproptosis and its relevance to cardiovascular diseaseBiomedicine & Pharmacotherapy, 2023
- The association between serum copper and obesity and all-cause mortality: the NHANES 2011–2016Environmental Science and Pollution Research, 2022
- What do we know about nutrient-based strategies targeting molecular mechanisms associated with obesity-related fatty liver disease?Annals of Hepatology, 2022
- Sinapic acid restores blood parameters, serum antioxidants, and liver and kidney functions in obesityJournal of Diabetes & Metabolic Disorders, 2022
- The combination of disulfiram and copper for cancer treatmentDrug Discovery Today, 2020
- Nonalcoholic Fatty Liver Disease Review: Diagnosis, Treatment, and OutcomesClinical Gastroenterology and Hepatology, 2015
- Copper: Effects of Deficiency and Overload2013