Role of metalloproteinases in the development and healing of acetic acid-induced gastric ulcer in rats.
OBJECTIVE
Matrix metalloproteinases (MMPs) are believed to be active in connective tissue remodeling associated with various physiological processes and in pathological conditions such as cancer and arthritis. However, the role of MMPs in gastrointestinal ulceration has not been clearly established. Therefore, the aim of this study was to examine the role of collagenase and gelatinases A and B in the development and healing of acetic acid-induced gastric ulcer in rats.


METHODS
Gastric ulcer was induced by injecting 20 microliters glacial acetic acid into gastric wall of rat stomachs. To examine whether changes in the ulcer formation and healing phase correlate with MMP activity, Triton X-100/CaCl2 and Tris/CaCl2 (60 degrees C) extracts of stomachs were prepared from controls and animals killed 24 h (formation phase) and 7 days (healing phase) after acetic acid administration. Total collagenase and gelatinase activities were measured using (H3)labeled-acetylated type I collagen or gelatin as substrate, respectively, prepared from rat skin.


RESULTS
Twenty-four hours after administration of acetic acid, the mean area of ulcer crater was 51.2 mm2. By day 7, the mean size of ulcer crater was reduced to 35.9 mm2. The mean activity of collagenase in gastric tissue from controls animals was 0.007 U/g tissue. In acetic acid-treated rats, this activity increased to 2.18 U/g at 24 h and declined to 0.69 U/g by day 7. Similarly, total gelatinase activity increased from 20.5 U/g tissue (controls) to 28.8 U/g at 24 h and declined to 23.9 U/g at day 7. Gelatinzymography revealed that gelatinase B levels were greatly increased at 24 h and declined by day 7, whereas the gelatinase A levels remained constant.


CONCLUSIONS
The data showed that the formation of acetic acid-induced ulcer in rats is accompanied by an elevation of collagenase and gelatinase B that gradually tend to return to control values during the healing phase.
Baragi
V M
VM
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
Qiu
L
L
Gunja-Smith
Z
Z
Woessner
J F
JF
Lesch
C A
CA
Guglietta
A
A
D019342:Acetic Acid / Q000633:toxicity; D000818:Animals; D017364:Collagenases / Q000378:metabolism; D003238:Connective Tissue / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018093:Gelatinases / Q000378:metabolism; D007202:Indicators and Reagents / Q000633:toxicity; D008297:Male; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology*
D007202:Indicators and Reagents; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019342:Acetic Acid