PMID- 34163351 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210625 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 12 DP - 2021 TI - Dietary Inorganic Nitrate Protects Hepatic Ischemia-Reperfusion Injury Through NRF2-Mediated Antioxidative Stress. PG - 634115 LID - 10.3389/fphar.2021.634115 [doi] LID - 634115 AB - Objectives: Hepatic ischemia-reperfusion injury (HIRI) is of common occurrence during liver surgery and liver transplantation and may cause hepatic impairment, resulting in acute liver dysfunction. Nitrate plays an important physiological regulatory role in the human body. Whether dietary nitrate could prevent HIRI is, however, unknown. Methods: A HIRI mouse model was established in that the blood supply to the median lobe and left lateral lobe was blocked for 60 min through the portal vein and related structures using an atraumatic clip. Sodium nitrate (4 mM) was administrated in advance through drinking water to compare the influence of sodium nitrate and normal water on HIRI. Results: Liver necrosis and injury aggravated after HIRI. The group treated with sodium nitrate showed the lowest activities of plasma aminotransferase and lactate dehydrogenase and improved outcomes in histological investigation and TUNEL assay. Mechanistically, sodium nitrate intake increased plasma and liver nitric oxide levels, upregulated nuclear factor erythroid 2-related factor 2 (NRF2)-related molecules to reduce malondialdehyde level, and increased the activities of antioxidant enzymes to modulate hepatic oxidative stress. Conclusions: Dietary inorganic nitrate could prevent HIRI, possibly by activating the NRF2 pathway and modulating oxidative stress. Our study provides a novel therapeutic compound that could potentially prevent HIRI during liver transplantation or hepatic surgery. CI - Copyright (c) 2021 Li, Jin, Sun, Zhang, Wang, Xu, Zhang and Wang. FAU - Li, Shaorong AU - Li S AD - Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology, Beijing, China. AD - Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Jin, Hua AU - Jin H AD - Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China. AD - Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China. FAU - Sun, Guangyong AU - Sun G AD - Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China. AD - Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China. FAU - Zhang, Chunmei AU - Zhang C AD - Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology, Beijing, China. AD - Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Wang, Jinsong AU - Wang J AD - Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology, Beijing, China. AD - Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing, China. FAU - Xu, Hufeng AU - Xu H AD - Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China. AD - Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China. FAU - Zhang, Dong AU - Zhang D AD - Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China. AD - Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China. FAU - Wang, Songlin AU - Wang S AD - Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health, Capital Medical University School of Stomatology, Beijing, China. AD - Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China. AD - Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing, China. LA - eng PT - Journal Article DEP - 20210607 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8215696 OTO - NOTNLM OT - NRF2 OT - hepatic ischemia reperfusion injury (HIRI) OT - nitrate OT - oral administration OT - oxidative stress COIS- 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- 2021/06/25 06:00 MHDA- 2021/06/25 06:01 PMCR- 2021/06/07 CRDT- 2021/06/24 06:33 PHST- 2020/11/27 00:00 [received] PHST- 2021/03/08 00:00 [accepted] PHST- 2021/06/24 06:33 [entrez] PHST- 2021/06/25 06:00 [pubmed] PHST- 2021/06/25 06:01 [medline] PHST- 2021/06/07 00:00 [pmc-release] AID - 634115 [pii] AID - 10.3389/fphar.2021.634115 [doi] PST - epublish SO - Front Pharmacol. 2021 Jun 7;12:634115. doi: 10.3389/fphar.2021.634115. eCollection 2021.