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Boric Acid Alleviates Gastric Ulcer by Regulating Oxidative Stress and Inflammation-Related Multiple Signaling Pathways

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Abstract

Oxidative stress and inflammation have pivotal roles in gastric ulcer development caused by alcohol consumption. Trace element boric acid taken into the human and animal body from dietary sources displays strong antioxidant and anti-inflammatory functions. However, the mechanisms underlying these actions of boric acid remain unclear, and its effectiveness in preventing gastric lesions is unknown. Therefore, the present study was undertaken to evaluate the protective effects of boric acid in alcohol-induced gastric ulcer and elucidate its potential mechanisms. Gastric ulcer was induced by 75% oral ethanol administration in rats, and the effectiveness of prophylactic boric acid treatment at 100 mg/kg concentration was assessed by histopathological examination, ELISA assay and qRT-PCR. Gross macroscopic and histopathological evaluations revealed that boric acid alleviated gastric mucosal lesions. Boric acid decreased reactive oxygen species (ROS) and malondialdehyde (MDA) concentration and the overall oxidation state of the body while improving antioxidant status. It reduced the concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The mRNA expression of JAK2 and STAT3 was decreased while the expression of AMPK was increased with boric acid pretreatment. Moreover, Sema3A and PlexinA1 levels were elevated upon boric acid pretreatment, and homocysteine levels were reduced. Our results demonstrated that boric acid protects gastric mucosa from ethanol-induced damage by regulating oxidative and inflammatory responses. In addition, our findings suggested that the gastroprotective activity of boric acid could be attributed to its regulatory function in the IL-6/JAK2/STAT3 signaling modulated by AMPK and that Sema3A/PlxnA1 axis and homocysteine are potentially involved in this process.

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Data will be made available on request.

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Funding

This study was supported by the of Kütahya Health Sciences University Scientific Research Projects, Kütahya, Turkey with the grant numbers FBA-2021-88.

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Authors and Affiliations

  1. Department of Histology and Embryology, Faculty of Medicine, Kütahya Health Sciences University, Kütahya, Türkiye

    Ayşe Çakır Gündoğdu

  2. Department of Medical Biology, Faculty of Medicine, Kütahya Health Sciences University, Kütahya, Türkiye

    Cansu Özbayer

  3. Department of Medical Biochemistry, Faculty of Medicine, Kütahya Health Sciences University, Evliya Çelebi Campus, 10th km of the Tavşanlı Road, 43100, Kütahya, Türkiye

    Fatih Kar

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Contributions

FK designed and managed the study. All authors participated equally in performing experiments, carrying out analysis, and interpreting the results. ACG drafted the manuscript and FK and CO revised critically the article.

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Correspondence to Fatih Kar.

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Gündoğdu, A.Ç., Özbayer, C. & Kar, F. Boric Acid Alleviates Gastric Ulcer by Regulating Oxidative Stress and Inflammation-Related Multiple Signaling Pathways. Biol Trace Elem Res 202, 2124–2132 (2024). https://doi.org/10.1007/s12011-023-03817-7

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