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Naloxone exerts a dose-dependent gastric cytoprotective effect
R L Kleiman1, K S Ephgrave, C G Adair
1College of Pharmacy, University of Iowa, Iowa City 52242.
Acta Physiologica Hungarica
|January 1, 1989
Summary
Naloxone demonstrates gastric cytoprotective properties against stress-induced ulcers in rats. This effect, observed with both intragastric and intravenous administration, correlates with dosage but not gastric acidity.
Area of Science:
- Pharmacology
- Gastroenterology
- Toxicology
Background:
- Previous studies indicated naloxone's inhibition of indomethacin and stress-induced gastric ulcers.
- The specific site, mechanism, and effective dosage of naloxone for gastric protection remained unclear.
Purpose of the Study:
- To investigate the gastric cytoprotective properties of naloxone.
- To establish a dose-response relationship for intragastric (IG) and intravenous (IV) naloxone administration in a rat model of gastric ulceration.
Main Methods:
- 102 rats were subjected to restraint stress at 4°C for 4 hours.
- Naloxone was administered hourly at doses of 0, 1, 5, 10, and 20 mg/kg (IG or IV).
- Gastric volume, pH, and mucosal lesion counts were assessed post-sacrifice.
Main Results:
- Naloxone significantly reduced gastric mucosal lesions compared to controls (p = 0.0001).
- Intravenous administration showed a greater protective effect than intragastric (p = 0.038).
- The cytoprotective effect correlated positively with naloxone dosage but not with changes in gastric acidity.
Conclusions:
- Naloxone exhibits significant gastric cytoprotective effects against stress-induced ulcers in rats.
- The protective mechanism is dose-dependent and route-dependent (IV > IG).
- Naloxone's gastric protection does not appear to be mediated by alterations in gastric acidity.