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

Abstract

This study investigated the potential of gadolinium chloride (GdCl 3 ), 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. GdCl 3 (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 GdCl 3 treatment inhibited dose-dependently superoxide anion (O 2 •− ), alkaline phosphatase (ALP), and MPO release and promoted neutrophil apoptosis. In vivo, low-dose GdCl 3 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, GdCl 3 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 GdCl 3 suggests its consideration as a beneficial tool in attenuating colon inflammation.

Thyme (Thymus vulgaris L.) polyphenols ameliorate DSS-induced ulcerative colitis of mice by mitigating intestinal barrier damage, regulating gut microbiota, and suppressing TLR4/NF-κB-NLRP3 inflammasome pathways

“…It is well known that the MPO activity and NO content are important indicators to assess the degree of neutrophil infiltration. 29 As can be seen from Fig. 3C and D, MPO and NO, as the important inflammatory mediators in colon tissues, were markedly increased ( p < 0.001) by 392.03% and 382.20% after DSS treatment, respectively.…”

Trypsin inhibitor LH011 inhibited DSS-induced mice colitis via alleviating inflammation and oxidative stress

“…LH011 or SASP also significantly reduced the mRNA levels of IL-1β, IL-6, and TNF-α in colonic tissues ( Figures 2D–F ). The degree of neutrophil infiltration could be determined by MPO activity index ( Ferrat et al, 2018 ). As shown in Figure 2G , compared with the control group, MPO activity was significantly higher after DSS stimulation.…”