Sara S Aboelmagd, Dina M Khodeer, Ahmed E Khodir, Naglaa F El-Orabi
{"title":"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","authors":"Sara S Aboelmagd, Dina M Khodeer, Ahmed E Khodir, Naglaa F El-Orabi","doi":"10.1007/s10787-025-01948-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>The primary aim of this study was to assess the protective effects of nifuroxazide at three different doses against indomethacin-induced GU.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Sara S Aboelmagd, Dina M Khodeer, Ahmed E Khodir, Naglaa F El-Orabi\",\"doi\":\"10.1007/s10787-025-01948-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>The primary aim of this study was to assess the protective effects of nifuroxazide at three different doses against indomethacin-induced GU.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":13551,\"journal\":{\"name\":\"Inflammopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2025-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Inflammopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10787-025-01948-y\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Inflammopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10787-025-01948-y","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
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.
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 [...]
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