Resveratrol Alleviates NEFA-Induced Oxidative Damage in Bovine Mammary Epithelial Cells by Restoring Mitochondrial Function
In periparturient dairy cows, high non-esterified fatty acids (NEFAs) caused by a severe negative energy balance induce oxidative stress and metabolic dysfunction, which pose a severe challenge to the dairy industry. Resveratrol (RES) is a polyphenolic compound with antioxidant, anti-inflammatory an...
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2025-01-01
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| author | Longwei Sun Junpeng Huang Xiangyang Dou Zhenyu Dong Yuan Li Shujing Tan Ran Yu Chengmin Li Weiguo Zhao |
| author_facet | Longwei Sun Junpeng Huang Xiangyang Dou Zhenyu Dong Yuan Li Shujing Tan Ran Yu Chengmin Li Weiguo Zhao |
| author_sort | Longwei Sun |
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| description | In periparturient dairy cows, high non-esterified fatty acids (NEFAs) caused by a severe negative energy balance induce oxidative stress and metabolic dysfunction, which pose a severe challenge to the dairy industry. Resveratrol (RES) is a polyphenolic compound with antioxidant, anti-inflammatory and multiple other physiological effects. However, its effect on oxidative damage triggered by NEFAs in bovine mammary epithelial cells is rarely reported. This study aimed to investigate the antioxidant effects and underlying molecular mechanisms of RES in NEFA-challenged BMECs. The results showed that RES ameliorated NEFA-induced oxidative damage by upregulating antioxidant enzyme expression and reducing malondialdehyde (MDA) and reactive oxygen species (ROS). Furthermore, exogenous NEFAs resulted in a decrease in mitochondrial membrane potential (MMP), cellular adenosine triphosphate (ATP) production, energy metabolism (NAD<sup>+</sup>/NADH ratio), abnormal mitochondrial structure and an increase in apoptosis levels. RES treatment restored mitochondrial function in NEFA-stressed BMECs, as evidenced by the increase in MMP, ATP generation and NAD<sup>+</sup>/NADH ratio accompanying the decline in mitochondrial structural abnormalities and cell apoptosis. In addition, in vivo studies in a mouse model of oxidative damage induced by high-fat diet (HFD) demonstrated that RES alleviated oxidative damage (decreased MDA content) and mitochondrial dysfunction (decreased expression of Drp1 and Fis1 and increased levels of Mfn2, Cyt C mRNA and ATP production) in mammary gland tissue. Overall, these findings suggested that RES could alleviate NEFA-induced oxidative damage in BMECs by modulating mitochondrial function, thereby contributing to the prevention and treatment of oxidative damage in perinatal dairy cows with a negative energy balance. |
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| spelling | doaj-art-4dd1678f801c435b9ba56dac840436da2025-01-24T13:17:38ZengMDPI AGAnimals2076-26152025-01-0115211810.3390/ani15020118Resveratrol Alleviates NEFA-Induced Oxidative Damage in Bovine Mammary Epithelial Cells by Restoring Mitochondrial FunctionLongwei Sun0Junpeng Huang1Xiangyang Dou2Zhenyu Dong3Yuan Li4Shujing Tan5Ran Yu6Chengmin Li7Weiguo Zhao8Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaJiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, ChinaIn periparturient dairy cows, high non-esterified fatty acids (NEFAs) caused by a severe negative energy balance induce oxidative stress and metabolic dysfunction, which pose a severe challenge to the dairy industry. Resveratrol (RES) is a polyphenolic compound with antioxidant, anti-inflammatory and multiple other physiological effects. However, its effect on oxidative damage triggered by NEFAs in bovine mammary epithelial cells is rarely reported. This study aimed to investigate the antioxidant effects and underlying molecular mechanisms of RES in NEFA-challenged BMECs. The results showed that RES ameliorated NEFA-induced oxidative damage by upregulating antioxidant enzyme expression and reducing malondialdehyde (MDA) and reactive oxygen species (ROS). Furthermore, exogenous NEFAs resulted in a decrease in mitochondrial membrane potential (MMP), cellular adenosine triphosphate (ATP) production, energy metabolism (NAD<sup>+</sup>/NADH ratio), abnormal mitochondrial structure and an increase in apoptosis levels. RES treatment restored mitochondrial function in NEFA-stressed BMECs, as evidenced by the increase in MMP, ATP generation and NAD<sup>+</sup>/NADH ratio accompanying the decline in mitochondrial structural abnormalities and cell apoptosis. In addition, in vivo studies in a mouse model of oxidative damage induced by high-fat diet (HFD) demonstrated that RES alleviated oxidative damage (decreased MDA content) and mitochondrial dysfunction (decreased expression of Drp1 and Fis1 and increased levels of Mfn2, Cyt C mRNA and ATP production) in mammary gland tissue. Overall, these findings suggested that RES could alleviate NEFA-induced oxidative damage in BMECs by modulating mitochondrial function, thereby contributing to the prevention and treatment of oxidative damage in perinatal dairy cows with a negative energy balance.https://www.mdpi.com/2076-2615/15/2/118resveratrolNEFAoxidative damagemitochondriabovine mammary epithelial cells |
| spellingShingle | Longwei Sun Junpeng Huang Xiangyang Dou Zhenyu Dong Yuan Li Shujing Tan Ran Yu Chengmin Li Weiguo Zhao Resveratrol Alleviates NEFA-Induced Oxidative Damage in Bovine Mammary Epithelial Cells by Restoring Mitochondrial Function Animals resveratrol NEFA oxidative damage mitochondria bovine mammary epithelial cells |
| title | Resveratrol Alleviates NEFA-Induced Oxidative Damage in Bovine Mammary Epithelial Cells by Restoring Mitochondrial Function |
| title_full | Resveratrol Alleviates NEFA-Induced Oxidative Damage in Bovine Mammary Epithelial Cells by Restoring Mitochondrial Function |
| title_fullStr | Resveratrol Alleviates NEFA-Induced Oxidative Damage in Bovine Mammary Epithelial Cells by Restoring Mitochondrial Function |
| title_full_unstemmed | Resveratrol Alleviates NEFA-Induced Oxidative Damage in Bovine Mammary Epithelial Cells by Restoring Mitochondrial Function |
| title_short | Resveratrol Alleviates NEFA-Induced Oxidative Damage in Bovine Mammary Epithelial Cells by Restoring Mitochondrial Function |
| title_sort | resveratrol alleviates nefa induced oxidative damage in bovine mammary epithelial cells by restoring mitochondrial function |
| topic | resveratrol NEFA oxidative damage mitochondria bovine mammary epithelial cells |
| url | https://www.mdpi.com/2076-2615/15/2/118 |
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