PMID- 36565836 OWN - NLM STAT- MEDLINE DCOM- 20230120 LR - 20230120 IS - 1879-0003 (Electronic) IS - 0141-8130 (Linking) VI - 228 DP - 2023 Feb 15 TI - Sodium butyrate protects against rotavirus-induced intestinal epithelial barrier damage by activating AMPK-Nrf2 signaling pathway in IPEC-J2 cells. PG - 186-196 LID - S0141-8130(22)03130-0 [pii] LID - 10.1016/j.ijbiomac.2022.12.219 [doi] AB - Rotavirus (RV) mainly infects intestinal epithelial cells, which leads to diarrhea in newborn piglets with dysfunction in the intestinal mucosal mechanical barrier. Sodium butyrate (SB) is one of the metabolites excreted by gut microbes. However, the protective effect of SB on RV infection induced intestinal mucosal mechanical barrier injury and its potential mechanism has not been well elucidated. In the present study, IPEC-J2 cells with RV infection was a model of intestinal mucosal mechanical barrier injury. Our results demonstrated that the appropriate concentration of SB can effectively alleviate TJ structural damage and up-regulating the expression of TJ-related genes. Furthermore, the appropriate concentration of SB can effectively reverse the increase of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) level induced by RV infection. Meanwhile, the levels of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-px) and antioxidant proteins NAD(P)H dehydrogenase quinone 1 (NQO1) and heme oxygenase-1 (HO-1) were increased through SB treatment. In addition, we found that SB increased cellular antioxidant capacity by activating the adenosine monophosphate-activated protein kinase (AMPK)-nuclear factor erythroid 2-related factor (Nrf2) signaling pathway and the cytoprotective effect of SB is limited by GPR109A siRNA. Thus, our findings revealed that SB reduces oxidative stress caused by RV infection and restores the intestinal mucosal mechanical barrier function by activating the AMPK-Nrf2 signal pathway mediated by the receptor GPR109A. CI - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Dong, Xia AU - Dong X AD - College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, PR China. FAU - Wang, Yi AU - Wang Y AD - College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, PR China. FAU - Zhu, Xiaoxiao AU - Zhu X AD - College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, PR China. FAU - Shen, Linyuan AU - Shen L AD - College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, PR China. FAU - Chen, Lei AU - Chen L AD - College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, PR China. FAU - Niu, Lili AU - Niu L AD - College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, PR China. FAU - Gan, Mailin AU - Gan M AD - College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, PR China. FAU - Zhang, Shunhua AU - Zhang S AD - College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, PR China. FAU - Zhang, Ming AU - Zhang M AD - College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, PR China. FAU - Jiang, Jun AU - Jiang J AD - College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, PR China. FAU - Chen, Daiwen AU - Chen D AD - Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China. FAU - Zhu, Li AU - Zhu L AD - College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, PR China. Electronic address: zhuli@sicau.edu.cn. FAU - Zhao, Ye AU - Zhao Y AD - College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, PR China. Electronic address: zhye@sicau.edu.cn. LA - eng PT - Journal Article DEP - 20221222 PL - Netherlands TA - Int J Biol Macromol JT - International journal of biological macromolecules JID - 7909578 RN - 0 (Antioxidants) RN - 0 (NF-E2-Related Factor 2) RN - 107-92-6 (Butyric Acid) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - Animals MH - Swine MH - *Antioxidants/pharmacology/metabolism MH - NF-E2-Related Factor 2/metabolism MH - *Rotavirus MH - Butyric Acid/pharmacology MH - AMP-Activated Protein Kinases/metabolism MH - Oxidative Stress MH - Signal Transduction MH - Epithelial Cells/metabolism OTO - NOTNLM OT - IPEC-J2 cells OT - Intestinal mucosal mechanical barrier OT - Oxidative stress OT - Rotavirus OT - Sodium butyrate COIS- Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/12/25 06:00 MHDA- 2023/01/21 06:00 CRDT- 2022/12/24 19:14 PHST- 2022/10/27 00:00 [received] PHST- 2022/12/18 00:00 [revised] PHST- 2022/12/19 00:00 [accepted] PHST- 2022/12/25 06:00 [pubmed] PHST- 2023/01/21 06:00 [medline] PHST- 2022/12/24 19:14 [entrez] AID - S0141-8130(22)03130-0 [pii] AID - 10.1016/j.ijbiomac.2022.12.219 [doi] PST - ppublish SO - Int J Biol Macromol. 2023 Feb 15;228:186-196. doi: 10.1016/j.ijbiomac.2022.12.219. Epub 2022 Dec 22.