Systemic phosphatidylcholine pretreatment protects canine esophageal mucosa during acute experimental biliary reflux.
OBJECTIVE
To characterize the consequences of short-term exposure to luminal bile on mucosal mast cell reactions in a canine model, and to determine the effects of systemic phosphatidylcholine pretreatment in this condition.


METHODS
Twenty mongrel dogs were used for experiments. Group 1 (n = 5) served as a saline-treated control, while in group 2 (n = 5) the esophagus was exposed to bile for 3 h. In group 3 (n = 5) the animals were pretreated with 7-nitroindazole to inhibit the neuronal isoform of nitric oxide synthase. In group 4 (n = 5) phosphatidylcholine solution (50 mg/kg) was administered iv before the biliary challenge. Mucosal microcirculation was observed by intravital videomicroscopy. Myeloperoxidase and nitric oxide synthase activities, the degrees of mast cell degranulation and mucosal damage were evaluated via tissue biopsies.


RESULTS
Exposure to bile evoked significant mast cell degranulation and leukocyte accumulation. The red blood cell velocity and the diameter of the postcapillary venules increased significantly. The tissue ATP content and constitutive nitric oxide synthase activity decreased, while the inducible nitric oxide synthase activity increased significantly as compared to the control values. 7-nitroindazole treatment significantly exacerbated the mucosal mast cell degranulation and tissue damage. In contrast, phosphatidylcholine pretreatment prevented the bile-induced ATP depletion, the inducible nitric oxide synthase and myeloperoxidase activity and the mast cell degranulation increased.


CONCLUSIONS
The neuronal nitric oxide synthase--mast cell axis plays an important role in the esophageal mucosal defense system. Systemic phosphatidylcholine pretreatment affords effective protection through ameliorating the bile-induced ATP depletion and secondary inflammatory reaction.
Institute of Surgical Research, University of Szeged, P O Box 427, H-6701 Szeged, Hungary.
Gabor
G
Eros
Jozsef
J
Kaszaki
Miklos
M
Czobel
Mihaly
M
Boros
D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001646:Bile; D015550:Cell Degranulation; D004285:Dogs; D004942:Esophagitis, Peptic / Q000517:prevention & control*; D004947:Esophagus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000502:physiology; D009092:Mucous Membrane / Q000187:drug effects; D020556:Neutrophil Infiltration; D052248:Nitric Oxide Synthase Type I / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D010713:Phosphatidylcholines / Q000627:therapeutic use*
D010713:Phosphatidylcholines; D000255:Adenosine Triphosphate; D009195:Peroxidase; D052248:Nitric Oxide Synthase Type I