PMID- 37884440 OWN - NLM STAT- MEDLINE DCOM- 20231030 LR - 20231030 IS - 1476-4954 (Electronic) IS - 1476-4954 (Linking) VI - 36 IP - 2 DP - 2023 Dec TI - Omeprazole activates aryl hydrocarbon receptor to reduce hyperoxia-induced oxidative stress in the peripheral blood mononuclear cells from premature infants. PG - 2272577 LID - 10.1080/14767058.2023.2272577 [doi] AB - OBJECTIVE: To investigate the correlation between the aryl hydrocarbon receptor (AhR) and reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) of premature infants, to demonstrate the protective role of AhR against hyperoxia-induced oxidative stress in premature infants and to provide a rational basis for the use of omeprazole (OM) as a new treatment for bronchopulmonary dysplasia (BPD). METHODS: From January 2021 to June 2021, 1-3 ml of discarded peripheral blood was collected from premature infants of gestational age less than 32 weeks who were not taking inhaled oxygen and were admitted to the Department of Neonatology of the Affiliated Hospital of Southwest Medical University. Using a random number table, the PBMCs were randomly assigned to each of the following groups: the control group, air + OM group, hyperoxia group, and hyperoxia + OM group. After 48 h of in vitro modeling and culture, PBMCs and the culture medium of each group were collected. Immunofluorescence analysis was used to examine ROS levels in PBMCs. A full-spectrum spectrophotometer was used to examine malondialdehyde (MDA) levels in the culture medium. Enzyme-linked immunosorbent assay (ELISA) was used to examine monocyte chemotactic protein 1 (MCP-1) levels in culture medium. Immunofluorescence analysis was used to examine the intracellular localization of AhR. Western blotting was used to examine the expression level of AhR in PBMCs. RESULTS: Compared with those in the control group, the levels of ROS, MDA, and MCP-1 and the cytoplasm-nuclear translocation rate of AhR in the air + OM group did not change significantly (p > 0.05), but the expression level of AhR increased significantly (p < 0.05). The levels of ROS, MDA, and MCP-1 and the cytoplasm-nuclear translocation rate of AhR significantly increased in the hyperoxia group (p < 0.05), and the expression level of AhR was significantly reduced (p < 0.05). Compared with those in the hyperoxia group, the levels of ROS, MDA, and MCP-1 in the hyperoxia + OM group were significantly reduced (p < 0.05), and the cytoplasm-nuclear translocation rate of AhR and the expression level of AhR were significantly increased (p < 0.05), but did not reach the level of the control group (p < 0.05). CONCLUSION: OM can activate AhR to inhibit hyperoxia-induced oxidative stress in the PBMCs from premature infants. FAU - Yang, Xi AU - Yang X AD - Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Sichuan Clinical Research Centre for Birth Defects, Luzhou, China. FAU - Bao, Zhengrong AU - Bao Z AD - Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Sichuan Clinical Research Centre for Birth Defects, Luzhou, China. FAU - Lei, Xiaoping AU - Lei X AD - Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Sichuan Clinical Research Centre for Birth Defects, Luzhou, China. FAU - Wang, Xia AU - Wang X AD - Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Sichuan Clinical Research Centre for Birth Defects, Luzhou, China. FAU - Zhao, Shuai AU - Zhao S AD - Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Sichuan Clinical Research Centre for Birth Defects, Luzhou, China. FAU - Du, Fengling AU - Du F AD - Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Sichuan Clinical Research Centre for Birth Defects, Luzhou, China. FAU - Liu, Xingling AU - Liu X AUID- ORCID: 0000-0003-2460-1671 AD - Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Sichuan Clinical Research Centre for Birth Defects, Luzhou, China. FAU - Dong, Wenbin AU - Dong W AD - Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Sichuan Clinical Research Centre for Birth Defects, Luzhou, China. LA - eng PT - Journal Article DEP - 20231026 PL - England TA - J Matern Fetal Neonatal Med JT - The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians JID - 101136916 RN - 0 (Reactive Oxygen Species) RN - KG60484QX9 (Omeprazole) RN - 0 (Receptors, Aryl Hydrocarbon) SB - IM MH - Humans MH - Infant, Newborn MH - Infant MH - *Hyperoxia/complications MH - Reactive Oxygen Species/metabolism MH - Omeprazole/pharmacology/therapeutic use MH - Receptors, Aryl Hydrocarbon/metabolism MH - Leukocytes, Mononuclear/metabolism MH - Infant, Premature MH - Oxidative Stress MH - Lung/metabolism OTO - NOTNLM OT - AhR OT - Omeprazole OT - ROS OT - oxidative stress OT - premature infants EDAT- 2023/10/27 00:43 MHDA- 2023/10/30 06:47 CRDT- 2023/10/26 22:03 PHST- 2023/10/30 06:47 [medline] PHST- 2023/10/27 00:43 [pubmed] PHST- 2023/10/26 22:03 [entrez] AID - 10.1080/14767058.2023.2272577 [doi] PST - ppublish SO - J Matern Fetal Neonatal Med. 2023 Dec;36(2):2272577. doi: 10.1080/14767058.2023.2272577. Epub 2023 Oct 26.