PMID- 37201406 OWN - NLM STAT- MEDLINE DCOM- 20230616 LR - 20230616 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 120 DP - 2023 Jul TI - Fucoidan mitigates gastric ulcer injury through managing inflammation, oxidative stress, and NLRP3-mediated pyroptosis. PG - 110335 LID - S1567-5769(23)00658-6 [pii] LID - 10.1016/j.intimp.2023.110335 [doi] AB - This study aimed to elucidate the gastro-protective effect of fucoidan against ethanol-induced gastric ulcer mediated via NLRP3-induced pyroptosis as an underlying mechanism, not yet assessed in prior research. Forty-eight male Albino mice were divided into six groups: Group I (normal control), group II (Ulcer/ethanol control), group III (Omeprazole + ethanol), group IV (fucoidan 25 mg + ethanol), group V (fucoidan 50 mg + ethanol) and group VI (fucoidan only). Fucoidan was administered orally for seven consecutive days followed by ulcer induction by a single oral dose of ethanol. Using colorimetric analysis, ELISA, qRT-PCR, histological assessment, and immunohistochemical studies, the results revealed that ethanol-induced ulcer exhibited an ulcer score of 42.5 +/- 5.1 and a significant increase (p < 0.05) in malondialdehyde (MDA), nuclear factor kappa B (NF-kappaB), and interleukin 6 (IL-6) with a significant decrease in the gastro-protective mediators, prostaglandin E2 (PGE2), superoxide dismutase (SOD) and glutathione (GSH), accompanied with an increase in NLRP3, interleukin 1beta (IL-1beta), interleukin 18 (IL-18), caspase 1, caspase 11, gasdermin D, and toll-like receptor 4 (TLR4), compared with the normal control. Pre-treatment with fucoidan showed a comparable result with omeprazole. Additionally, pre-treatments elevated the levels of the gastro-protective mediators and lessened oxidative stress, relative to the positive control findings. Conclusively, fucoidan has a promising gastro-protective role by inhibiting inflammation and pyroptosis. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Selim, Hend Mostafa AU - Selim HM AD - Biochemistry Department, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt. FAU - Negm, Walaa A AU - Negm WA AD - Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt. FAU - Hawwal, Mohammed F AU - Hawwal MF AD - Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 4545, Saudi Arabia. FAU - Hussein, Ismail A AU - Hussein IA AD - Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt. FAU - Elekhnawy, Engy AU - Elekhnawy E AD - Pharmaceutical Microbiology Department, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt. FAU - Ulber, Roland AU - Ulber R AD - Institute of Bioprocess Engineering, Rheinland-Pfalzische Technische Universitat Kaiserslautern-Landau, Gottlieb-Daimler-Strasse 49, 67663 Kaiserslautern, Germany. FAU - Zayed, Ahmed AU - Zayed A AD - Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt; Institute of Bioprocess Engineering, Rheinland-Pfalzische Technische Universitat Kaiserslautern-Landau, Gottlieb-Daimler-Strasse 49, 67663 Kaiserslautern, Germany. Electronic address: ahmed.zayed1@pharm.tanta.edu.eg. LA - eng PT - Journal Article DEP - 20230516 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 9072-19-9 (fucoidan) RN - GAN16C9B8O (Glutathione) RN - KG60484QX9 (Omeprazole) RN - 3K9958V90M (Ethanol) RN - 0 (NF-kappa B) SB - IM MH - Mice MH - Animals MH - Male MH - *Stomach Ulcer/chemically induced/drug therapy/pathology MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Ulcer/metabolism MH - Pyroptosis MH - Gastric Mucosa MH - Oxidative Stress MH - Inflammation/metabolism MH - Glutathione/metabolism MH - Omeprazole/therapeutic use/pharmacology MH - Ethanol/metabolism MH - NF-kappa B/metabolism OTO - NOTNLM OT - Ethanol OT - Fucoidan OT - Gastro-protective OT - Inflammation OT - NLRP3 OT - Pyroptosis OT - Ulcer 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- 2023/05/19 01:04 MHDA- 2023/06/16 06:42 CRDT- 2023/05/18 18:07 PHST- 2023/02/20 00:00 [received] PHST- 2023/04/28 00:00 [revised] PHST- 2023/05/10 00:00 [accepted] PHST- 2023/06/16 06:42 [medline] PHST- 2023/05/19 01:04 [pubmed] PHST- 2023/05/18 18:07 [entrez] AID - S1567-5769(23)00658-6 [pii] AID - 10.1016/j.intimp.2023.110335 [doi] PST - ppublish SO - Int Immunopharmacol. 2023 Jul;120:110335. doi: 10.1016/j.intimp.2023.110335. Epub 2023 May 16.