Gastroprotective effect of nifuroxazide against indomethacin-induced gastric ulcers in rats via modulation of Nrf2/HO-1, HMGB1/TLR4/NF-κB p65, and apoptotic caspase-3 signaling pathways.

IF 5.3 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2025-09-24 DOI:10.1007/s10787-025-01948-y

Sara S Aboelmagd, Dina M Khodeer, Ahmed E Khodir, Naglaa F El-Orabi

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引用次数: 0

Abstract

Background: Gastric ulcer (GU) is a common gastrointestinal disease linked to the consumption of non-steroidal anti-inflammatory drugs (NSAIDs), with traditional therapies often causing several adverse effects and drug interactions.

Aim: The primary aim of this study was to assess the protective effects of nifuroxazide at three different doses against indomethacin-induced GU.

Methods: Rats were pretreated orally once daily for 14 days with either nifuroxazide (10, 20, or 40 mg/kg) or famotidine (25 mg/kg), the standard reference drug. After 24 h of fasting, a single oral dose of 50 mg/kg indomethacin was used to induce GU. Six hours later, rats were anesthetized using ketamine.

Results: Nifuroxazide dose-dependently mitigated the rise in ulcer index, retained gastric mucin content, and alleviated histopathological changes. These gastroprotective effects were due to the attenuation of oxidative stress, evidenced by reduced malondialdehyde (MDA) levels and increased levels of reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Furthermore, nifuroxazide lessened gastric mucosal inflammation by lowering gastric high mobility group box 1 protein (HMGB1), nuclear factor kappa B p65 (NF-κB p65), tumor necrosis factor-alpha (TNF-α), and signal transducer and activator of transcription 3 (STAT3) levels, toll-like receptor 4 (TLR4) and interleukin-1 beta (IL-1β) expressions, as well as serum levels of C-reactive protein (CRP). In addition, nifuroxazide mitigated apoptosis by inhibiting immunohistochemical expression of caspase-3.

Conclusions: Nifuroxazide has the potential to be repurposed as a novel gastroprotective therapy that restores gastric mucosal barrier integrity via the mitigation of gastric oxidative stress, inflammation, and apoptosis.

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硝呋噻嗪通过调节Nrf2/HO-1、HMGB1/TLR4/NF-κB p65和凋亡caspase-3信号通路对吲哚美辛诱导大鼠胃溃疡的胃保护作用

背景：胃溃疡（GU）是一种常见的胃肠道疾病，与非甾体抗炎药（NSAIDs）的使用有关，传统的治疗方法经常引起一些不良反应和药物相互作用。目的：本研究的主要目的是评估三种不同剂量硝呋沙嗪对吲哚美辛诱导的GU的保护作用。方法：采用标准对照药法莫替丁（25 mg/kg）或硝呋噻嗪（10、20、40 mg/kg），每日口服1次，连续14 d。禁食24 h后，单次口服50 mg/kg吲哚美辛诱导GU。6小时后，用氯胺酮麻醉大鼠。结果：硝呋沙嗪剂量依赖性地减轻了溃疡指数升高，保留了胃粘蛋白含量，减轻了组织病理改变。这些胃保护作用是由于氧化应激的减弱，其证据是丙二醛（MDA）水平降低，还原型谷胱甘肽（GSH）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、核因子红系2相关因子2 （Nrf2）和血红素加氧酶-1 （HO-1）水平升高。此外，nifuroxazide通过降低胃高迁移性组盒1蛋白（HMGB1）、核因子κB p65 （NF-κB p65）、肿瘤坏死因子-α (TNF-α)、信号传导和转录激活因子3 （STAT3）水平、toll样受体4 （TLR4）和白细胞介素-1β (IL-1β)表达以及血清c反应蛋白（CRP）水平，减轻胃粘膜炎症。此外，nifuroxazide通过抑制caspase-3的免疫组织化学表达来减轻细胞凋亡。结论：Nifuroxazide有潜力被重新用作一种新的胃保护疗法，通过减轻胃氧化应激、炎症和细胞凋亡来恢复胃粘膜屏障的完整性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]