Salicylate enhances rat gastric gelatinase activity.
BACKGROUND
Increased matrix metalloproteinase (MMP) activity is associated with tissue injury in some organs. Their role in gut injury remains to be fully elucidated. We recently demonstrated that increased MMP-2 activity participated in lipopolysaccharide (LPS)-induced gastric injury. Thus we hypothesized that MMPs may play a role in other models of gastric injury.


METHODS
The effect of L-NAME (10 mg/kg IP) or salicylate (100 mg/kg IP) on gastric injury from 20% ethanol was evaluated in an anesthetized model of gastric injury. In a separate experiment, gastric metalloproteinase activity was assessed after salicylate or L-NAME administration. Rats were given either L-NAME (10 mg/kg), salicylate (100 mg/kg), or saline IP and sacrificed after 6 hours. Gastric mucosa was harvested and portions of the glandular stomach snap frozen for gelatin and in situ zymography as indices of MMP activity. Subsequently the effect of MMP inhibition on macroscopic gastric injury from salicylate and a dilute luminal irritant was determined.


RESULTS
Both L-NAME and salicylate significantly increased gastric injury from 20% ethanol versus saline controls. Salicylate treatment significantly increased gelatinase activity as determined by in situ zymography and gelatin zymography while L-NAME did not. MMP inhibition ameliorated macroscopic gastric injury secondary to salicylate and a dilute luminal irritant.


CONCLUSIONS
This is the first study to report that MMP activity increases in the stomach following salicylate treatment. These data suggest that MMPs may play a role in the ability of salicylate to exacerbate gastric injury from irritants, but likely do not play a role in mediating the deleterious effects of L-NAME.
Robinson
Emily K
EK
Department of Surgery at the University of Texas Health Science Center Houston, USA. emily.k.robinson@uth.tmc.edu
West
Sonlee D
SD
Mercer
David W
DW
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology*; D005780:Gelatin / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism*; D007509:Irritants / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000494:pharmacology*; D013656:Taurocholic Acid / Q000494:pharmacology
D002492:Central Nervous System Depressants; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007509:Irritants; D012459:Salicylates; D000431:Ethanol; D013656:Taurocholic Acid; D005780:Gelatin; D018093:Gelatinases; D019331:NG-Nitroarginine Methyl Ester