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Published on: March 1, 2024
Salicylate enhances rat gastric gelatinase activity
Emily K Robinson1, Sonlee D West, David W Mercer
1Department of Surgery at the University of Texas Health Science Center Houston, USA. emily.k.robinson@uth.tmc.edu
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.
Materials And 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.
Insights
Salicylate increases gastric injury and matrix metalloproteinase (MMP) activity in the stomach. MMP inhibition reduced this salicylate-induced injury, suggesting MMPs contribute to gastric damage.
Area of Science:
- Gastroenterology
- Biochemistry
- Pharmacology
Background:
- Matrix metalloproteinase (MMP) activity is linked to tissue injury in various organs, but its role in gut injury requires further investigation.
- Previous research indicated MMP-2 activity contributes to lipopolysaccharide-induced gastric injury.
- This study hypothesized that MMPs play a role in other gastric injury models.
Purpose of the Study:
- To investigate the role of matrix metalloproteinases (MMPs) in salicylate- and L-NAME-induced gastric injury.
- To determine the effect of MMP inhibition on gastric injury caused by salicylate and luminal irritants.
Main Methods:
- Gastric injury was induced by ethanol in rats treated with L-NAME or salicylate.
- Gastric metalloproteinase activity was assessed using gelatin zymography and in situ zymography.
- The impact of MMP inhibition on salicylate-induced gastric injury was evaluated.
Main Results:
- Both L-NAME and salicylate treatments significantly exacerbated ethanol-induced gastric injury.
- Salicylate administration led to a significant increase in gelatinase activity, unlike L-NAME.
- Inhibition of MMPs effectively reduced macroscopic gastric injury caused by salicylate and irritants.
Conclusions:
- This study is the first to demonstrate increased MMP activity in the stomach after salicylate treatment.
- The findings suggest that MMPs contribute to salicylate's exacerbation of gastric injury from irritants.
- MMPs do not appear to mediate the harmful effects of L-NAME on the stomach.
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