Mast cell stabilization prevents ethanol-induced rat gastric mucosal injury: mechanisms of protection.
BACKGROUND
We previously demonstrated that 60% ethanol increased macromolecular leakage and induced lesion formation in areas of permanent flow stasis within gastric mucosal vessels. Mast cells and their mediators have been implicated in acute mucosal injury. Fluorescent in vivo microscopy was used to assess the effects of ketotifen, a mast cell stabilizer, and pyrilamine, a histamine (H1)-receptor antagonist, on ethanol-induced rat gastric mucosal injury.


METHODS
Experiments were carried out on anaesthetized rats pretreated orally with ketotifen (1 mg/kg) or pyrilamine (30 mg/kg). Fluorescein isothiocyanate-bovine serum albumin (FITC-BSA; 0.2 mL/100 g), a marker for quantitating macromolecular leakage was administered intra-arterially. Ethanol (60%) or distilled water was applied topically to the gastric mucosa. Macromolecular leakage of FITC-BSA, vessel diameters and leucocyte activity were quantified using image analysis.


RESULTS
Pretreatment with ketotifen or pyrilamine, followed by ethanol, caused no change in macromolecular leakage compared with controls. Both compounds prevented blood flow stasis in all areas and no lesion formation was observed. However, increased leucocyte activity and increases in vessel diameter were observed following pretreatment with ketotifen and pyrilamine, respectively.


CONCLUSIONS
The data suggest that vasoactive substances released from mast cells may be involved in the aetiology of ethanol-induced gastric mucosal damage. The prevention of these normal physiological responses to injury may lead to the employment of other microcirculatory mechanisms of defence.
Kalia
N
N
Department of Surgical and Anaesthetic Sciences, Royal Hallamshire Hospital, Sheffield, United Kingdom. N.Kalia@sheffield.ac.uk
Bardhan
K D
KD
Reed
M W
MW
Jacob
S
S
Brown
N J
NJ
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D008833:Microcirculation / Q000187:drug effects; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D006634:Histamine H1 Antagonists; D000431:Ethanol; D011738:Pyrilamine; D007665:Ketotifen