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Gadolinium chloride attenuates acetic acid-evoked colitis in mice by reducing neutrophil infiltration and pro-oxidative enzyme activity

  • Meriem Ferrat
  • Hichem MoulahoumEmail author
  • Belkacem Mohamed Amine Boumaza
  • Souad Mouzaoui
  • Axel Périanin
  • Bahia DjerdjouriEmail author
Original Article
  • 35 Downloads

Abstract

This study investigated the potential of gadolinium chloride (GdCl3), an inhibitor of kupffer cells on the myeloperoxidase (MPO) function, both in vivo on colon inflammation model and in vitro on thioglycollate-elicited peritoneal neutrophils. Colon inflammation was induced in mice (n = 7) by 4% acetic acid (AA) enema. GdCl3 (10 mg/kg) treatment was given 24 h before AA challenge. Clinical changes during the protocol were scored. Colons were segmented into distal and proximal parts for histological and biochemical assessment. Furthermore, myeloperoxidase (MPO) enzymes were extracted and analyzed by western blot. Short-term GdCl3 treatment inhibited dose-dependently superoxide anion (O2·−), alkaline phosphatase (ALP), and MPO release and promoted neutrophil apoptosis. In vivo, low-dose GdCl3 improved colitis scores and inhibited acute phagocyte recruitment and colon damage within the mucosa as revealed by the decrease in MPO, nitric oxide (NO), and malondialdehyde (MDA) levels. At the same time, GdCl3 restored catalase (CAT), superoxide dismutase (SOD) activities, and reduced glutathione (GSH) levels, thus reversing the MDA/GSH ratio in both distal and proximal colons. Compared to proximal, distal colon was more altered and displayed higher pathological manifestations. Lastly, the induction of apoptosis and regulation of the major nitrosative and oxidative functions of neutrophils by GdCl3 suggests its consideration as a beneficial tool in attenuating colon inflammation.

Keywords

Colitis Gadolinium chloride Myeloperoxidase Apoptosis Nitro-oxidative stress 

Abbreviations

ALP

Alkaline phosphatase

AO

Acridine orange hemi(zinc chloride) salt

CAT

Catalase

C5a

Complement fraction 5a

Ca2+

Calcium

Col

Colitis

CD

Crohn disease

DAI

Disease activity index

fMLP

Formyl-methionyl-leucyl-phenylalanine

GdCl3

Gadolinium(III) chloride

GSH

Reduced glutathione

H2O2

Hydrogen peroxide

HBSS

Hanks’ balanced salt solution

HEPES

4-(2-Hydroxyethyl) piperazine-1-ethanesulfonic acid

H&E

Hematoxylin and eosin

IBD

Inflammatory bowel disease

IL-8

Interleukin-8

iNOS

Inducible nitric oxide synthase

INFγ

Interferon gamma

LPS

Lipopolysaccharides

LTB4

Leukotriene B4

MTT

Methylthiazol tetrazolium

MPO

Myeloperoxidase

NBT

Nitrotetrazolium blue chloride

NO

Nitric oxide

NF-κB

Nuclear factor-kappa B

PAF

Platelet-activating factor

PBS

Phosphate buffer saline

PMA

Phorbol 12-myristate 13-acetate

PN

Polynuclear neutrophils

PNC

Platelet-neutrophil complexes

pNPP

p-Nitrophenol-phosphate

PSGL-1

P-selectin glycoprotein ligand-1

ROS

Reactive oxygen species

SOD

Superoxide dismutase

SDS

Sodium dodecyl sulfate

TBA

Thiobarbituric acid

TNF-α

Tumor necrosis factor-alpha

UC

Ulcerative colitis

Notes

Acknowledgments

This study was supported by the Research project “Implication of phagocytes-dependent oxidative stress in inflammatory diseases and leishmaniasis” with project no. CNEPRU F00220130061, Algerian Ministry of Higher Education and Scientific Research.

Author contribution

MF, SM, AP, and BD conceived and designed the research plan. MF, HM, and BMAB conducted animal experiments. MF, SM, and AP conducted in vitro protocols. MF, HM, and BMAB analyzed the data. MF wrote the manuscript. SM, AP, and BD supervised the work and revised the manuscript. All authors read and approved the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Cell and Molecular Biology, Faculty of Biological SciencesUniversity of Sciences and Technology Houari Boumediene (USTHB)AlgiersAlgeria
  2. 2.INSERM UMRS-1149, Faculté de Médecine X. BichatParisFrance
  3. 3.CNRS ERL 8252, Centre de Recherche sur l’InflammationParisFrance

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