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Chunlan Xu, Lei Qiao, Li Ma, Yu Guo, Xina Dou, Shuqi Yan, Baohua Zhang, Alexandra RomanThe Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, Shaanxi, People’s Republic of ChinaBackground: Selenium (Se) can exert antioxidative activity and prevent the body from experiencing oxidative injury. Biogenic Se nanoparticles (SeNPs) synthesized by probiotics possess relatively strong chemical stability, high bioavailability, and low toxicity, this makes them potential Se supplements. Previously, we demonstrated that SeNPs synthesized by Lactobacillus casei ATCC 393 can alleviate hydrogen peroxide (H2O2)-induced human and porcine intestinal epithelial cells’ oxidative damage. However, the antioxidant mechanism remains unclear.Methods: The possible antioxidant mechanism and protective effect of SeNPs on intestinal epithelial permeability and mitochondrial function were evaluated by establishing an H2O2-induced oxidative damage model of human colon mucosal epithelial cells (NCM460) and conducting Nrf2 inhibitor interference experiments. Mitochondrial membrane potential (MMP), mitochondrial DNA content, adenosine triphosphate (ATP), ROS, and protein expression levels of Nrf2-related genes were determined. Mitochondrial ultrastructure was visualized by transmission electron microscopy.Results: An amount of 4 μg Se/mL of SeNPs synthesized by L. casei ATCC 393 alleviated increase of ROS, reduced ATP and MMP, and maintained intestinal epithelial permeability in NCM460 cells challenged by H2O2. In addition, SeNPs improved the protein levels of Nrf2, HO-1, and NQO-1. Moreover, SeNPs attenuated the damage of mitochondrial ultrastructure caused by oxidative stress. Nrf2 inhibitor (ML385) abolished the regulatory effect of SeNPs on intracellular ROS production.Conclusion: Data suggest that biogenic SeNPs synthesized by L. casei ATCC 393 can protect the intestinal epithelial barrier function against oxidative damage by alleviating ROS-mediated mitochondrial dysfunction via Nrf2 signaling pathway. Biogenic SeNPs are an attractive candidate for potential Se supplement agent in preventing oxidative stress-related intestinal disease by targeting mitochondria.Keywords: Lactobacillus casei, selenium nanoparticles, mitochondrial, antioxidant, reactive oxygen species, intestinal barrier