Topical and intravenous administration of trefoil factors protect the gastric mucosa from ethanol-induced injury in the rat.
BACKGROUND
hTFF2 and pTFF2 (formerly PSP and hSP, respectively) are members of the trefoil factor family (TFF) and are distributed throughout the gastrointestinal tract in both normal and diseased tissue. Trefoil factors have been shown to exert a mucosal protectant and/or healing role in a number of animal models but controversy exists surrounding this property in relation to their dose and route of administration.


OBJECTIVE
To investigate the effects of topically applied and intravenously infused trefoil factors (hTFF2 and pTFF2) and prostaglandin E2 on ethanol-induced gastric mucosal damage in rats.


METHODS
A gastric chamber preparation in the anaesthetized rat was used. Injury was caused by exposing the gastric mucosa to absolute ethanol for 1 min. Trefoil factors or prostaglandin E2 were administered either intravenously or topically before and after the introduction of absolute ethanol onto the gastric mucosa. Damage was assessed by measurement of gastric mucosal Na+ leakage and area of macroscopic injury.


RESULTS
Like prostaglandin E2, intravenous administration of hTFF2 and pTFF2 reduced both the gastric mucosal Na+ leakage and the mean area of damage caused by ethanol. Similarly, treatment of the gastric mucosa with topical application of hTFF2 at doses of 120 microg/kg and above reduced the Na+ leakage and the area of damage. pTFF2 at 120 microg/kg and 1.2 mg/kg applied topically produced a marked reduction in total area of damage.


CONCLUSIONS
Intravenously infused hTFF2 and pTFF2 protect the gastric mucosa from ethanol-induced damage in the anaesthetized rat. In addition, topical application of trefoil factors also was effective at protecting the gastric mucosa from injury at doses lower than previously reported.
McKenzie
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Gastrointestinal Pharmacology Unit, Biosciences Division, University of Hertfordshire, Hatfield, UK. c.mckenzie@mds.qmw.ac.uk
Thim
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Parsons
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ME
D000287:Administration, Topical; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006133:Growth Substances / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3
D002492:Central Nervous System Depressants; D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; C099037:TFF3 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D000431:Ethanol; D015232:Dinoprostone