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


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.


Colitis Gadolinium chloride Myeloperoxidase Apoptosis Nitro-oxidative stress 



Alkaline phosphatase


Acridine orange hemi(zinc chloride) salt




Complement fraction 5a






Crohn disease


Disease activity index




Gadolinium(III) chloride


Reduced glutathione


Hydrogen peroxide


Hanks’ balanced salt solution


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


Hematoxylin and eosin


Inflammatory bowel disease




Inducible nitric oxide synthase


Interferon gamma




Leukotriene B4


Methylthiazol tetrazolium




Nitrotetrazolium blue chloride


Nitric oxide


Nuclear factor-kappa B


Platelet-activating factor


Phosphate buffer saline


Phorbol 12-myristate 13-acetate


Polynuclear neutrophils


Platelet-neutrophil complexes




P-selectin glycoprotein ligand-1


Reactive oxygen species


Superoxide dismutase


Sodium dodecyl sulfate


Thiobarbituric acid


Tumor necrosis factor-alpha


Ulcerative colitis



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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