Evidence map›Paper›PMID 41024762›Full record

ArticleWorld journal of gastroenterology2025

Ambroxol mitigates cyclophosphamide-induced liver injury by suppressing TLR-4/NF-κB signaling and oxidative stress and upregulating cytoglobin, TXNRD1 and HMGB1.

Reem S Alruhaimi, Emad H M Hassanein, Sulaiman M Alnasser, Ahmad F Ahmeda, Hanan S Althagafy, Omnia A M Abd El-Ghafar, Ayman M Mahmoud

Abstract read
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Article in World journal of gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Reem S AlruhaimiDepartment of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
Emad H M HassaneinDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt.
Sulaiman M AlnasserDepartment of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 52571, Saudi Arabia.
Ahmad F AhmedaDepartment of Basic Medical Sciences, College of Medicine, Ajman University, Ajman 346, United Arab Emirates.
Hanan S AlthagafyDepartment of Biochemistry, Faculty of Science, University of Jeddah, Jeddah 21589, Saudi Arabia.
Omnia A M Abd El-GhafarDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef 62571, Egypt.
Ayman M MahmoudDepartment of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester M1 5GD, United Kingdom. a.mahmoud@mmu.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCyclophosphamide (CP) is a potent chemotherapeutic and immunosuppressant agent, but its hepatotoxicity remains a significant concern. Ambroxol (ABX) is a mucolytic agent with emerging beneficial effects against oxidative stress and inflammation.

aimTo investigate the hepatoprotective effects of ABX against CP-induced liver injury, focusing on oxidative stress, inflammation, and the possible role of cytoglobin, thioredoxin reductase 1 (TXNRD1) and high-mobility group box 1 (HMGB1).

methodsABX (20 mg/kg) was orally administered for 7 days, and the rats received a single injection of CP (100 mg/kg) on day 5. Blood and liver samples were collected for analyses, and the affinity of ABX towards cytoglobin, TXNRD1, and HMGB1 was evaluated using molecular docking.

resultsCP administration significantly elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, reduced albumin, and caused multiple histopathological alterations in the liver. ABX effectively restored liver function biomarkers and attenuated histopathological alterations. CP-induced oxidative stress was evidenced by increased malondialdehyde and decreased glutathione and antioxidant enzyme activities, all of which were ameliorated by ABX. CP upregulated toll-like receptor 4 (TLR-4), nuclear factor-kappaB (NF-κB) p65 and pro-inflammatory cytokines, while downregulating cytoglobin, TXNRD1 and HMGB1. ABX suppressed TLR-4/NF-κB signaling and pro-inflammatory cytokines, and upregulated cytoglobin, TXNRD1 and HMGB1.

conclusionABX protects against CP hepatotoxicity by mitigating oxidative stress, suppressing TLR-4/NF-κB signaling, and upregulating cytoglobin, TXNRD1 and HMGB1. ABX showed binding affinity towards cytoglobin, TXNRD1 and HMGB1. These findings suggest that ABX has therapeutic potential in alleviating hepatotoxicity associated with CP treatment.

Indexed as

AmbroxolChemical and Drug Induced Liver InjuryCyclophosphamideAnimalsCytoglobinDisease Models, AnimalHMGB1 ProteinHumansLiverMaleMolecular Docking SimulationNF-kappa BOxidative StressRatsRats, Sprague-DawleySignal TransductionAmbroxolCyclophosphamideCygb protein, ratCytoglobinHbp1 protein, ratHMGB1 ProteinNF-kappa BTlr4 protein, ratToll-Like Receptor 4Acute liver injuryAmbroxolChemotherapyCyclophosphamideHepatotoxicityInflammationOxidative stress

Identifiers

PMID41024762
PMCPMC12476691

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.