Fucoidin Prevents Clostridium difficile Toxin-A-Induced Ileal Enteritis in Mice

Abstract

Recent reports suggest increased incidence and severity of Clostridium difficile-associated diseases. These facts have raised the need for additional clarification of pathogenesis and for a search for new therapeutic strategies. This study evaluated the effects of the polysaccharide fucoidin, an L-selectin blocker, on toxin-A-induced mouse enteritis. Fucoidin (25 mg/kg) or saline (0.1 ml) were injected systemically (ocular plexus) 5 min prior to local challenge with toxin A (5 microg/ileal loop) or phosphate-buffered saline (PBS). Intestinal fluid volume/length and ileal loop weight/length ratios were calculated 3 h later. Ileal tissues were collected for histopathology and measurement of myeloperoxidase and adenosine deaminase activity. Fucoidin significantly (P < 0.05) prevented the toxin-A-induced increase in weight/length and volume/length ratios and reduced mucosal disruption, as shown in histopathology. Fucoidin also significantly (P < 0.05) reduced toxin-A-induced myeloperoxidase and adenosine deaminase activities. In conclusion, fucoidin reduces tissue injury and inflammation in toxin-A-induced mouse enteritis.

Adenosine Deaminase Inhibition PreventsClostridium difficileToxin A-Induced Enteritis in Mice

“…We now show that in the presence of EHNA, the effects of ATL313 are much weaker than when the agonist is used alone, which indicates that most of the anti-inflammatory effects of EHNA observed in our model rely on its ability to enhance the concentration of adenosine in the ileal tissue that maximally stimulates A2A receptors. The abundant presence of neutrophils within TxA-induced pseudomembranes is well known (9,34), as is their important role in the pathogenesis of ileal damage induced by C. difficile TxA (2,27). Here, we showed that EHNA reduced TxA-induced MPO activity, suggesting a potent effect of EHNA to inhibit neutrophil infiltration into ileal tissue.…”

A MLST Clade 2 Clostridium difficile strain with a variant TcdB induces severe inflammatory and oxidative response associated with mucosal disruption

“…Samples were evaluated for the severity of epithelial damage, edema, neutrophil infiltration, and hemorrhage, using a scale ranging from 0 (absence of alterations) to 3 (severe) [34].…”

Protective Effects of Fucoidan, a P- and L-Selectin Inhibitor, in Murine Acute Pancreatitis

“…Natural products have been increasingly exploited as a source of therapeutic compounds for a variety of diseases, and interest has recently focused on the properties of sulfated fucans. 13,14 However, as yet, no studies concerning the potential effects of fucoidan in acute pancreatitis have been published. 10,11 Fucoidan has been shown to act as a ligand for either L-or P-selectin, thereby inhibiting leukocyte rolling.…”