Endometritis is a common inflammatory condition of the uterine endometrial lining that primarily affects perinatal dairy animals and causes significant economic losses in agriculture. It is usually triggered by pathogenic bacteria and is associated with chronic postpartum reproductive tract infections. Bacterial lipopolysaccharides (LPSs) are known to increase levels of reactive oxygen species (ROS), leading to oxidative stress and inflammation through the activation of the NF-κB signaling pathway and the inhibition of Nrf2 nuclear translocation, which regulates antioxidant response elements (AREs). The effectiveness of the conventional management strategy involving antibiotics is decreasing due to resistance and residual concerns. This review explores the potential therapeutic benefits of targeting the Nrf2/Kelch-like ECH-associated protein 1 (Keap1)/NF-κB signaling pathway to alleviate LPS-induced endometritis. We discuss recent advancements in veterinary medicine that utilize exogenous antioxidants to modulate these pathways, thereby reducing oxidative stress and inflammatory responses in endometrial cells. This review highlights the efficacy of several bioactive compounds that enhance Nrf2 signaling and suppress NF-κB activation, offering protective effects against oxidative damage and inflammation. By examining various in vitro studies, this review emphasizes the emerging role of these signaling pathways in developing new therapeutic strategies that could potentially replace or supplement traditional treatments and mitigate the economic impacts of endometritis in livestock.
Keywords: Nrf2/Keap1/NF-κB signaling pathway; ROS; bioactive compounds; endometritis; inflammation; oxidative stress.