Increased gastroduodenal concentrations of transforming growth factor alpha in adaptation to aspirin in monkeys and rats.
OBJECTIVE
The mechanism by which gastric mucosa becomes more resistant to damage by repeated aspirin administration is not known. Transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) prevent drug-induced gastric injury. The aim of this study was to determine whether gastroduodenal tissue levels of TGF-alpha and EGF protein were altered during adaptation to aspirin-induced injury in monkeys and rats in vivo.


METHODS
Animals were given aspirin daily for up to 28 days. Gross mucosal injury was assessed by computerized image analysis in rats and by endoscopy in monkeys. Mucosal concentrations of TGF-alpha and EGF were quantitated by radioimmunoassays from endoscopic biopsy samples in monkeys and from scraped mucosa in rats.


RESULTS
Long-term administration of aspirin caused a significant increase in gastric and duodenal tissue levels of TGF-alpha in monkeys and rats; the increased levels of TGF-alpha significantly correlated with the decrease in aspirin-induced injury. No change in the gastroduodenal tissue levels of EGF was observed. Adaptation was not associated with any significant change in basal gastric acid secretion in monkeys and occurred despite a significant decrease in gastric mucin in rats.


CONCLUSIONS
Adaptation of the gastric mucosa to the damaging effect of aspirin is associated with a significant and specific increase in TGF-alpha protein in the gastroduodenum.
Romano
M
M
Department of Medicine (Gastroenterology), Vanderbilt University, Nashville, Tennessee, USA.
Lesch
C A
CA
Meise
K S
KS
Veljaca
M
M
Sanchez
B
B
Kraus
E R
ER
Boland
C R
CR
Guglietta
A
A
Coffey
R J
RJ
D000222:Adaptation, Physiological; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004815:Epidermal Growth Factor / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D009077:Mucins / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D012044:Regression Analysis; D013270:Stomach / Q000187:drug effects*; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009077:Mucins; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D001241:Aspirin