PMID- 38537540 OWN - NLM STAT- MEDLINE DCOM- 20240430 LR - 20240430 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 132 DP - 2024 May 10 TI - Protective effect of astaxanthin on ANCA-associated vasculitis. PG - 111928 LID - S1567-5769(24)00446-6 [pii] LID - 10.1016/j.intimp.2024.111928 [doi] AB - OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by inflammation and fibrinoid necrosis of medium and small vessels, and its pathogenesis is closely related to inflammation and oxidative stress. Astaxanthin (ATX) is a carotenoid with anti-inflammatory, antioxidant, and immunomodulatory effects. We hypothesized that ATX could play a role in AAV treatment. This study aimed to investigate whether ATX has a protective effect against AAV and to elucidate its regulatory mechanism. METHODS: In vitro experiments, neutrophils isolated from healthy people were treated with ATX or not and cultured with serum from myeloperoxidase (MPO) -ANCA-positive patients and healthy persons. The levels of IL-6 and TNF-alpha in neutrophil culture supernatant before and after stimulation were measured. Neutrophil extracellular traps (NETs) and intracellular reactive oxygen species (ROS) in neutrophils were detected after stimulation. In vivo study, experimental autoimmune vasculitis (EAV) rat models were established and then treated with ATX via intragastric administration for 6 consecutive weeks. Urinary erythrocytes, urinary proteins, and serum creatinine were detected and HE staining was performed to assess renal injury in rats. Lung hemorrhage was observed by gross dissection and microscopic Prussian blue staining. The level of serum MPO-ANCA was detected. Serum IL-6, TNF-alpha, superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) in rats were measured to explore the effects of ATX on oxidative stress and inflammation in EAV rats. The deposition of MPO in kidney and lung of rats was detected by immunohistochemistry. RESULTS: ATX significantly inhibited neutrophil secretion of inflammatory factors IL-6 and TNF-alpha. ATX reduced the elevated levels of ROS in neutrophils stimulated by serum from AAV patients and alleviated the release of NETs. ATX administration was observed to reduce the degree of hematuria, proteinuria, and glomerular crescent formation in EAV rats. The degree of pulmonary hemorrhage was significantly reduced. Besides, the serum levels of IL-6 and TNF-alpha were attenuated, and antioxidant SOD and GSH-px increased in serum. Pathological results showed that MPO deposition was decreased in lung and kidney tissues after ATX treatment. CONCLUSION: ATX could ameliorate the organ damages in EAV rats. It could serve as a hopeful therapy for AAV by its anti-inflammatory and anti-oxidative feature as a unique nature carotenoid. CI - Copyright (c) 2024 Elsevier B.V. All rights reserved. FAU - Sun, Ruo-Lan AU - Sun RL AD - Department of Renal Division, Affiliated Hospital of Qingdao University, Qingdao 266555, China. FAU - Shang, Jin-Chun AU - Shang JC AD - Department of Renal Division, Affiliated Hospital of Qingdao University, Qingdao 266555, China. FAU - Han, Run-Hong AU - Han RH AD - Department of Renal Division, Affiliated Hospital of Qingdao University, Qingdao 266555, China. FAU - Xing, Guang-Qun AU - Xing GQ AD - Department of Renal Division, Affiliated Hospital of Qingdao University, Qingdao 266555, China. Electronic address: gqx99monash@163.com. LA - eng PT - Journal Article DEP - 20240326 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 8XPW32PR7I (astaxanthine) RN - 0 (Xanthophylls) RN - EC 1.11.1.7 (Peroxidase) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Reactive Oxygen Species) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antibodies, Antineutrophil Cytoplasmic) SB - IM MH - Animals MH - *Xanthophylls/pharmacology/therapeutic use MH - *Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy/pathology/immunology MH - Humans MH - Male MH - *Neutrophils/immunology/drug effects MH - Rats MH - *Peroxidase/metabolism MH - *Interleukin-6/metabolism/blood MH - *Tumor Necrosis Factor-alpha/metabolism MH - Female MH - Reactive Oxygen Species/metabolism MH - Anti-Inflammatory Agents/therapeutic use/pharmacology MH - Disease Models, Animal MH - Oxidative Stress/drug effects MH - Cells, Cultured MH - Extracellular Traps/drug effects/metabolism MH - Kidney/drug effects/pathology/metabolism MH - Antibodies, Antineutrophil Cytoplasmic/immunology MH - Rats, Sprague-Dawley MH - Lung/pathology/drug effects/immunology MH - Middle Aged OTO - NOTNLM OT - Anti-neutrophil cytoplasmic antibody-associated vasculitis OT - Astaxanthin OT - Inflammation OT - Neutrophil extracellular traps OT - Oxidative stress COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/03/28 00:45 MHDA- 2024/04/30 06:45 CRDT- 2024/03/27 19:14 PHST- 2024/01/16 00:00 [received] PHST- 2024/03/12 00:00 [revised] PHST- 2024/03/22 00:00 [accepted] PHST- 2024/04/30 06:45 [medline] PHST- 2024/03/28 00:45 [pubmed] PHST- 2024/03/27 19:14 [entrez] AID - S1567-5769(24)00446-6 [pii] AID - 10.1016/j.intimp.2024.111928 [doi] PST - ppublish SO - Int Immunopharmacol. 2024 May 10;132:111928. doi: 10.1016/j.intimp.2024.111928. Epub 2024 Mar 26.