4.4 Article

High-salt diet contributes to excess oxidative stress and abnormal metabolism in mouse ovaries

Journal

BIOMEDICAL CHROMATOGRAPHY
Volume 36, Issue 12, Pages -

Publisher

WILEY
DOI: 10.1002/bmc.5500

Keywords

arachidonic acid; high-salt diet; NADPH oxidase; ovary; reactive oxygen species

Funding

  1. Postdoctoral Fellowship of Peking-Tsinghua Center for Life Sciences
  2. National Natural Science Foundation of China [31871482]

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High-salt diets cause elevated levels of reactive oxygen species (ROS) in ovarian tissue, leading to increased oxidative stress. This study found that ROS and H2O2 levels significantly increased in the ovaries of mice on a high-salt diet, along with enhanced antioxidant enzyme activity. However, the activation of antioxidant defense appeared insufficient to counterbalance the increased oxidative stress. In addition, high-salt diets significantly altered the metabolic patterns of ovarian tissue, mainly affecting fatty acid metabolism.
High-salt diets (HSDs) are associated with elevated levels of reactive oxygen species (ROS), which play a key role in ovarian disorders. However, it is not yet clear whether HSDs impact ovarian redox balance and metabolism. Accordingly, in this study, we analyzed the effect of HSDs on ovarian redox balance by biochemical analysis and further dissected its possible mechanism by metabolic analysis combined with the correlation network method. We found that ROS and H2O2 levels significantly increased in the ovarian tissue of mice receiving an HSD for 4 weeks. The enhanced activity of NADPH oxidase may contribute to an increase in ROS in ovarian tissue after excessive salt consumption. Meanwhile, the activities of key antioxidant enzymes, including superoxide dismutase 2, glutathione peroxidase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase, increased significantly. The apparent activation of antioxidant defense appeared insufficient as the glutathione, GSH/GSSG ratio, and NADPH/NADP(+) ratio decreased significantly. In addition, HSDs significantly altered the metabolic patterns of ovarian tissue in mice, and pathways were mainly enriched in fatty acid metabolism. Arachidonic acid was an altered hub metabolite according to Pearson correlation network analysis. Mechanistically, an HSD increased the concentration of arachidonic acid in ovarian tissue, inducing high NADPH oxidase activity, which increased the levels of ROS and H2O2. Our results indicate that HSDs can lead to increased oxidative stress and dramatically alter the metabolic patterns in mouse ovarian tissues.

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