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.
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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
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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.
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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.
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Ferrat, M., Moulahoum, H., Boumaza, B.M.A. et al. Gadolinium chloride attenuates acetic acid-evoked colitis in mice by reducing neutrophil infiltration and pro-oxidative enzyme activity. Naunyn-Schmiedeberg's Arch Pharmacol 392, 299–311 (2019). https://doi.org/10.1007/s00210-018-1592-3
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DOI: https://doi.org/10.1007/s00210-018-1592-3