Resveratrol Alleviates NEFA-Induced Oxidative Damage in Bovine Mammary Epithelial Cells by Restoring Mitochondrial Function
by
, and
Longwei Sun
1,2, 
Junpeng Huang
1,2,
Xiangyang Dou
1,2,
Zhenyu Dong
1,2,
Yuan Li
1,2,
Shujing Tan
1,2,
Ran Yu
1,2,
Chengmin Li
1,2,* and
Weiguo Zhao
1,2,* 1
Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China
2
Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, The Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang 212100, China
*
Authors to whom correspondence should be addressed.
Animals 2025, 15(2), 118; https://doi.org/10.3390/ani15020118
Submission received: 26 November 2024
/
Revised: 31 December 2024
/
Accepted: 2 January 2025
/
Published: 7 January 2025
(This article belongs to the Section Cattle)
Simple Summary
Resveratrol (RES), a polyphenolic compound, is known for its diverse bioactivities such as its antioxidant and antimicrobial properties. This study explored the antioxidant effects of RES on NEFA-induced BMECs. It focused on mitochondrial function using both in vitro and in vivo approaches. The results showed that RES effectively reduced oxidative stress, cell death and mitochondrial damage caused by elevated NEFA levels in bovine mammary cells, and enhanced antioxidant potential and mitochondrial function in mammary gland tissue. These findings suggest that RES could mitigate oxidative damage by modulating mitochondrial function.
Abstract
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+/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+/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.
