The role of mucosal mast cell degranulation and free-radical generation in intestinal ischaemia-reperfusion injury in rats.
OBJECTIVE
In this study, we determined the role of mucosal mast cell (MMC) activation in the pathogenesis of intestinal ischaemia-reperfusion (I/R) injury by immunohistochemical analysis using anti-RMCP II antibody. In addition, we investigated the role of free-radical generation in the activation of MMCs in this model.


METHODS
In the first experiment, rats were divided into four groups: (1) sham operated; (2) I/R + saline; (3) I/R + the mast cell stabilizer, MAR-99 (30 mg/kg); and (4) I/R + MAR-99 (100 mg/kg). Treatment with MAR-99 was started 1 h before the occlusion of the superior mesenteric artery (SMA). In the second experiment, rats were divided into five groups: (1) sham operated; (2) I/R + saline; (3) I/R + superoxide dismutase (SOD; 50,000 U/ml); (4) I/R + catalase (90,000 U/ml); and (5) I/R + allopurinol (50 mg/kg/day). Intravenous administration of SOD and catalase was performed 1 h before SMA occlusion. Oral administration of allopurinol was started 2 days before I/R surgery. We measured several parameters of intestinal mucosal injury and evaluated the degranulation of MMCs by using an immunohistochemical technique.


RESULTS
The number of resting MMCs, detected by anti-RMCP II antibody, was significantly decreased in the I/R-treated rats. The I/R treatment induced a decrease in the mucosal histamine content and an increase in plasma histamine levels. Mucosal permeability in the small intestine was significantly enhanced by I/R treatment. However, these changes were significantly prevented by pretreatment with the MMC stabilizer, MAR-99. Furthermore, administration of several free-radicals scavengers (SOD, catalase, and allopurinol) also blocked the I/R-induced degranulation of MMCs.


CONCLUSIONS
These data indicate that activation of MMCs was involved in the pathogenesis of I/R-induced intestinal mucosal injury. In addition, some parts of the I/R-induced MMC activation pathway were mediated by free-radical generation.
Kimura
T
T
Department of Internal Medicine, Shiga University of Medical Science, Tukinowa, Otsu, Japan.
Fujiyama
Y
Y
Sasaki
M
M
Andoh
A
A
Fukuda
M
M
Nakajima
S
S
Bamba
T
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D015550:Cell Degranulation; D005609:Free Radicals / Q000378:metabolism; D006632:Histamine / Q000097:blood; D007150:Immunohistochemistry; D007422:Intestines / Q000098:blood supply*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*
D000897:Anti-Ulcer Agents; D005609:Free Radicals; D011743:Pyrimidines; D006632:Histamine; C087838:MAR 99