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Humic Acid Has Protective Effect on Gastric Ulcer by Alleviating Inflammation in Rats

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Abstract

The new agents are needed in treatment of gastric ulcer that have less side effects, adequate efficacy, and no drug interactions. In this study, we aimed to investigate the potential protective effects of humic acid on experimental gastric ulcer. Wistar Albino male rats (n = 48) were randomly divided into 8 groups as follow; Control (without any applications), Humic acid (50 mg/kg), ethanol group (1 mL/rat), and indomethacin group (25 mg/kg). In the treatment groups, both gastric ulcer model and humic acid 50 mg/kg were applied. In addition, famotidine the antiulcer drug was used as positive control. All medications were administered by oral gavage. Levels of ADAM10 and ADAMTS12 in gastric mucosa were determined by ELISA method. Hematoxylin-Eosin (H&E) staining, iNOS, and PCNA immunohistochemical staining were performed for histopathological investigations. Apoptosis was demonstrated by using the TUNEL method. In addition, the levels of inflammatory cytokines (TNF-α, IL-6, IL-10) and caspase-3 gene were determined by qRT-PCR. ADAM10 and ADAMTS12 levels significantly increased in the treatment groups compared to the ulcer groups (p < 0.05). The experimental groups showed mucosal erosion, bleeding, leukocyte infiltration and edema. Treatment with humic acid and famotidine was found to suppress iNOS activity, thereby decreasing proinflammatory activity and preventing damage to the gastric mucosa, while reducing the number of apoptotic cells. IL-6, IL-10, TNF-α and caspase-3 levels were significantly decreased in the treatment groups compared to damaged gastric mucosa. As a result, humic acid may be defined as a potential protective agent with its anti-inflammatory effect in gastric ulcer.

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Funding

This study was supported by the Scientific Research Commission of Canakkale Onsekiz Mart University with the project named “Investigation of the Effects of Humic Acid in Different Acute Gastric Ulcer Models in Rats” coded TSA-2018-2592.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Faculty of Medicine, Çanakkale Onsekiz Mart University, 17100, Çanakkale, Turkey

    Müşerref Hilal Şehitoğlu

  2. Department of Biophysics, Faculty of Medicine, Çanakkale Onsekiz Mart University, 17100, Çanakkale, Turkey

    Özlem Öztopuz

  3. Department of Emergency and Disaster Management, School of Health, Edirne Namik Kemal University, 59030, Tekirdag, Turkey

    İhsan Karaboğa

  4. Department of Physiology, Faculty of Medicine, Çanakkale Onsekiz Mart University, 17100, Çanakkale, Turkey

    Mehmet Akif Ovalı & Metehan Uzun

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  1. Müşerref Hilal Şehitoğlu
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Correspondence to Müşerref Hilal Şehitoğlu.

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Statement on the welfare of animals. Our study was approved by Canakkale Onsekiz Mart University Animal Experiments Local Ethics Committee with decision 2018/05-02.

Highlights

Humic acid has a healing effect on stomach damage at the histopathological level, Humic acid suppresses iNOS and apoptosis and increases PCNA activity,

Humic acid reduces TNF-a and IL-6 levels that are proinflammatory cytokines in the gastric mucosa, while it increases IL-10 levels which is a member of anti-inflammatory cytokines, Humic acid increases ADAM10 and ADAMTS12 levels, these healing effects of humic acid are as strong as famotidine.

ADAMTS12 was also present in gastric mucosa for the first time, so ADAMTS12 levels were determined in healthy, gastric ulcer models and humic acid treated groups.

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Şehitoğlu, M.H., Öztopuz, Ö., Karaboğa, İ. et al. Humic Acid Has Protective Effect on Gastric Ulcer by Alleviating Inflammation in Rats. Cytol. Genet. 56, 84–97 (2022). https://doi.org/10.3103/S0095452722010091

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