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Preventive Anti-inflammatory Effects of Apocynin on Acetic Acid–Induced Colitis in Rats

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Abstract

Ulcerative colitis is an inflammatory bowel disease with a complex aetiology characterised by abnormal immune responses and oxidative stress–induced tissue injury. Inflammatory cells play an important role in the progression of this pathology through the overproduction of reactive oxygen species (ROS) from various sources including the NADPH oxidases (NOXs). The aim of this study was to investigate the preventive effect of apocynin, a natural antioxidant molecule and a selective inhibitor of NOXs, on acetic acid (AA)-induced ulcerative colitis in rats. Our results first confirmed that apocynin has a high free radical scavenging capacity as well as a potent iron chelating ability. Oral pretreatment of rats with apocynin (200 mg/kg and 400 mg/kg) for 7 days prior to AA-induced colitis suppressed the increase in pro-oxidant markers in colonic homogenates and preserved colonic cytoarchitecture from acetic acid–induced damage. Oral administration of apocynin (200 mg/kg and 400 mg/kg) also reduced several systemic inflammatory markers such as alkaline phosphatase, iron, pro-inflammatory cytokines, C-reactive protein and myeloperoxidase. This study shows that apocynin protects rats from acetic acid–induced colonic inflammation and suggests that apocynin may have a promising beneficial effect in the prevention of ulcerative colitis.

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DATA AVAILABILITY

All data generated during this study are included in this published version; for further details on data availability, please contact the corresponding author.

Abbreviations

AA:

Acetic acid

ABTS:

2,2′-Azino-bis-3-ethylbenzothiazoline-6-sulfonic acid

ALP:

Alkaline phosphatase

AOPPs:

Advanced oxidation protein products

AP:

Apocynin

BHT:

Butylated hydroxytoluene

CRP:

C-reactive protein

DAI:

Disease activity index

DMSO:

Dimethylsulfoxide

DPPH:

1,1-Diphenyl-2-picrylhydrazyl

DTNB:

5,5′-Dithiobis-(2-nitrobenzoic acid)

EDTA:

Ethylenediaminetetraacetic acid

ELISA:

Enzyme-linked immunosorbent assay

EM:

External mucosa

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

GSH:

Glutathione

H2O2 :

Hydrogen peroxide

HTAB:

Hexadecyltrimethylammonium bromide

IBD:

Inflammatory bowel disease

IC50 :

Half-maximal inhibitory concentration

IL-1β:

Interleukin-1β

iNOS:

Inducible nitric oxide synthase

L:

Length

LM:

Lamina

MDA:

Malondialdehyde

MM:

Muscularis mucosa

MPO:

Myeloperoxidase

NADPH:

Nicotinamide adenine dinucleotide phosphate oxidase

NOX:

NADPH oxidase

PBS:

Phosphate-buffered saline

ROS:

Reactive oxygen species

SM:

Submucosa

SOD:

Superoxide dismutase

SSZ:

Sulfasalazine

TBA:

Thiobarbituric acid

TCA:

Trichloroacetic acid

TNF-α:

Tumour necrosis factor-α

UC:

Ulcerative colitis

W:

Weight

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ACKNOWLEDGEMENTS

The authors would like to thank the INSERM, the CNRS, the University of Paris-cité, the LabEx Inflamex and the Tunisian DGRST for providing laboratory facilities during this study.

Funding

The research was funded by the INSERM, the CNRS, the City University of Paris and the DGRST of the Tunisian Ministry of Higher Education, Scientific Research and Technology.

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Author notes

  1. Mossadok Ben-Attia and Jamel El-Benna contributed equally to this work.

Authors and Affiliations

  1. INSERM-U1149, CNRS-ERL8252, Inflammation Research Center, Inflamex Excellence Laboratory, Xavier Bichat Faculty of Medicine, City University of Paris, Paris, F-75018, France

    Ahmed Kouki, Pham My-Chan Dang & Jamel El-Benna

  2. Environment Biomonitoring Laboratory (LR01/ES14), Sciences Faculty of Bizerta, University of Carthage, 7021, Zarzouna, Bizerte, Tunisia

    Ahmed Kouki, Wafa Ferjani, Abdelaziz Souli & Mossadok Ben-Attia

  3. Risks Related to Environmental Stress Unity (UR17/ES20), Department of Life Sciences, Bizerta Faculty of Sciences, University of Carthage, 7021, Zarzouna, Bizerte, Tunisia

    Néziha Ghanem-Boughanmi

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  1. Ahmed Kouki
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Contributions

A. K. contributed to the methodology, statistical analysis, animal experiments and drafting of the manuscript. W. F., P. M.-C. D., N. G.-B. and A. S. contributed to the data curation, formal analysis, critical revision, visualisation and validation. All authors read and approved the manuscript. J. E.-B. and M. B.-A. contributed to the study design, methodology, drafting, critical revision, editing and validation.

Corresponding author

Correspondence to Jamel El-Benna.

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Ethical Approval and Consent to Participate

The experimental protocols (No. 0123/2022 ATSAL) were approved by the Ethics Committee of the Tunisian Association of Laboratory Animal Sciences and were carried out in accordance with the European Community Council Directive of 24 November 1986. Consent to participate is not applicable.

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The authors declare no competing interests.

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Kouki, A., Ferjani, W., Dang, P.MC. et al. Preventive Anti-inflammatory Effects of Apocynin on Acetic Acid–Induced Colitis in Rats. Inflammation 47, 438–453 (2024). https://doi.org/10.1007/s10753-023-01920-4

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