PMID- 38050447 OWN - NLM STAT- MEDLINE DCOM- 20240118 LR - 20240118 IS - 1099-0461 (Electronic) IS - 1095-6670 (Linking) VI - 38 IP - 1 DP - 2024 Jan TI - Nanocurcumin attenuates pyroptosis and inflammation through inhibiting NF-kappaB/GSDMD signal in high altitude-associated acute liver injury. PG - e23606 LID - 10.1002/jbt.23606 [doi] AB - Exposure to a hypobaric hypoxic environment at high altitudes can lead to liver injury, and mounting evidence indicates that pyroptosis and inflammation play important roles in liver injury. Curcumin (Cur) can inhibit pyroptosis and inflammation. Therefore, our purpose here was to clarify the mechanism underlying the protective effect of nanocurcumin (Ncur) and Cur in a rat model of high altitude-associated acute liver injury. Eighty healthy rats were selected and exposed to different altitudes (6000 or 7000 m) for 0, 24, 48, or 72 h. Fifty normal healthy rats were divided into normal control, high-altitude control, salidroside (40 mg/kg [Sal-40]), Cur (200 mg/kg [Cur-200]), and Ncur (25 mg/kg [Ncur-25]) groups and exposed to a high-altitude hypobaric hypoxic environment (48 h, 7000 m). Serum-liver enzyme activities (alanine transaminase, aspartate transaminase, and lactate dehydrogenase were detected and histopathology of liver injury was evaluated by hematoxylin and eosin staining, and inflammatory factors were detected in liver tissues by enzyme-linked immunosorbent assays. Pyroptosis-associated proteins (gasdermin D, gasdermin D N-terminal [GSDMD-N], pro-Caspase-1, and cleaved-Caspase-1 [cleaved-Casp1]) and inflammation-associated proteins (nuclear factor-kappaB [NF-kappaB], phospho-NF-kappaB [P-NF-kappaB], and high-mobility group protein B1 [HMGB1]) levels were analyzed by immunoblotting. Ncur and Cur inhibited increased serum-liver enzyme activities, alleviated liver injury in rats caused by high-altitude hypobaric hypoxic exposure, and downregulated inflammatory factors, including tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-18, in rat liver tissues. The level of P-NF-kappaB, GSDMD-N, cleaved-Casp1, and HMGB1 in rat liver tissues increased significantly after high-altitude exposure. Ncur and Cur downregulated P-NF-kappaB, GSDMD-N, cleaved-Casp-1, and HMGB1. Ncur and Cur may inhibit inflammatory responses and pyroptosis in a rat model of high altitude-associated acute liver injury. CI - (c) 2023 The Authors. Journal of Biochemical and Molecular Toxicology published by Wiley Periodicals LLC. FAU - Yang, Xinyue AU - Yang X AUID- ORCID: 0000-0001-8230-1322 AD - Key Laboratory of Special Environmental Medicine of Xinjiang, General Hospital of Xinjang Military Command, Urumqi, China. AD - Graduate School, Xinjiang Medical University, Urumqi, China. FAU - Dong, Xiang AU - Dong X AUID- ORCID: 0000-0001-8690-7735 AD - Graduate School, Xinjiang Medical University, Urumqi, China. FAU - Li, Jiajia AU - Li J AUID- ORCID: 0000-0003-3406-9703 AD - Graduate School, Xinjiang Medical University, Urumqi, China. FAU - Zheng, Aiping AU - Zheng A AD - Institute of Pharmacology and Toxicology, Academy of Military Medicine, Beijing, China. FAU - Shi, Wenhui AU - Shi W AUID- ORCID: 0000-0002-4338-4046 AD - Graduate School, Xinjiang Medical University, Urumqi, China. FAU - Shen, Caifu AU - Shen C AUID- ORCID: 0000-0002-4656-5344 AD - Graduate School, Xinjiang Medical University, Urumqi, China. FAU - Liu, Jiangwei AU - Liu J AUID- ORCID: 0000-0002-7652-9379 AD - Graduate School, Xinjiang Medical University, Urumqi, China. LA - eng GR - 2019D04022/Xinjiang Uygur Autonomous Region Department of Education/ PT - Journal Article DEP - 20231204 PL - United States TA - J Biochem Mol Toxicol JT - Journal of biochemical and molecular toxicology JID - 9717231 RN - 0 (NF-kappa B) RN - 0 (HMGB1 Protein) RN - 0 (Gasdermins) RN - EC 3.4.22.36 (Caspase 1) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) SB - IM MH - Rats MH - Animals MH - NF-kappa B/metabolism MH - Pyroptosis MH - *HMGB1 Protein/metabolism MH - Altitude MH - Gasdermins MH - Inflammation/drug therapy/metabolism MH - *Liver Diseases/metabolism MH - Caspase 1/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism OTO - NOTNLM OT - acute liver injury OT - hypobaric hypoxia OT - inflammation OT - nanocurcumin OT - pyroptosis EDAT- 2023/12/05 12:42 MHDA- 2024/01/18 06:42 CRDT- 2023/12/05 03:44 PHST- 2023/07/12 00:00 [revised] PHST- 2022/05/07 00:00 [received] PHST- 2023/11/21 00:00 [accepted] PHST- 2024/01/18 06:42 [medline] PHST- 2023/12/05 12:42 [pubmed] PHST- 2023/12/05 03:44 [entrez] AID - 10.1002/jbt.23606 [doi] PST - ppublish SO - J Biochem Mol Toxicol. 2024 Jan;38(1):e23606. doi: 10.1002/jbt.23606. Epub 2023 Dec 4.