Cecropin A Alleviates LPS-Induced Oxidative Stress and Apoptosis of Bovine Endometrial Epithelial Cells

Simple Summary Dairy cows receiving a prolonged high-concentrate diet are highly susceptible to sub-acute ruminal acidosis, leading to an elevated concentration of lipopolysaccharides (LPSs) in the peripheral blood circulation. A high concentration of LPS can cause severe oxidative stress, leading to various inflammations, which can cause inflammatory damage and even apoptosis. Antimicrobial peptides (AMPs) not only have antimicrobial effects but also play roles in cells including anti-inflammation, antioxidative stress, and anti-apoptosis. In this study, we found that cecropin A, as an AMP, relieved LPS-induced oxidative stress in dairy cow endometrial epithelial cells and inhibited the inflammatory response caused by oxidative damage. Additionally, we discovered that cecropin A can effectively alleviate LPS-induced cell apoptosis by inhibiting the mitochondrial-dependent apoptotic pathway.Abstract Dairy cows receiving a prolonged high-concentrate diet express an elevated concentration of lipopolysaccharides (LPSs) in the peripheral blood circulation, accompanied by a series of systemic inflammatory responses; however, the specific impacts of inflammation are yet to be determined. Cecropin-like antimicrobial peptides have become a research hotspot regarding antimicrobial peptides because of their excellent anti-inflammatory activities, and cecropin A is a major member of the cecropin family. To elucidate the mechanism of cecropin A as anti-inflammatory under the condition of sub-acute ruminal acidosis (SARA) in dairy cows, we induced inflammation in bEECs with LPS (10 mu g/mL) and then added cecropin A (25 mu M). Afterwards, we detected three categories of indexes including oxidative stress indices, inflammation-related genes, and apoptosis-related genes in bovine endometrial epithelial cells (bEECs). The results indicated that cecropin A has the ability to reduce inflammatory factors TNF-alpha, IL-1 beta, and IL-8 and inhibit the MAPK pathway to alleviate inflammation. In addition, cecropin A is able to reduce reactive oxygen species (ROS) levels and alleviates LPS-induced oxidative stress and mitochondrial dysfunction by downregulating NADPH Oxidase (NOX), and upregulating catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Furthermore, cecropin A demonstrates the ability to inhibit apoptosis by suppressing the mitochondrial-dependent apoptotic pathway, specifically Fas/FasL-caspase-8/-3. The observed increase in the Bcl-2/Bax ratio, a known apoptosis regulator, further supports this finding. In conclusion, our study presents novel solutions for addressing inflammatory responses associated with SARA.