Gadolinium chloride attenuates acetic acid-evoked colitis in mice by reducing neutrophil infiltration and pro-oxidative enzyme activity.
Meriem FerratHichem MoulahoumBelkacem Mohamed Amine BoumazaSouad MouzaouiAxel PérianinBahia DjerdjouriPublished in: Naunyn-Schmiedeberg's archives of pharmacology (2018)
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.
Keyphrases
- oxidative stress
- cell cycle arrest
- induced apoptosis
- low dose
- cell death
- nitric oxide
- diabetic rats
- minimally invasive
- endoplasmic reticulum stress
- hydrogen peroxide
- pi k akt
- randomized controlled trial
- liver failure
- breast cancer cells
- type diabetes
- drug induced
- high dose
- mass spectrometry
- human health
- combination therapy
- high glucose
- respiratory failure
- magnetic resonance imaging
- amyotrophic lateral sclerosis
- cell proliferation
- risk assessment
- hepatitis b virus
- single molecule
- extracorporeal membrane oxygenation