Morphological features of rat gastric mucosa after acute and chronic treatment with amtolmetin guacyl: comparison with non-selective and COX-2-selective NSAIDs.
OBJECTIVE
The compound amtolmetin guacyl (AMG) has been characterized in both animal and human studies as a novel non-selective non-steroidal anti-inflammatory drug (NSAID) endowed with lower ulcerogenicity in comparison with traditional NSAIDs due to a unique mechanism of action, namely the increase in endogenous production of gastric nitric oxide.


METHODS
Conscious rats were treated either acutely (4 h) or chronically (3 and 14 days) with intragastric AMG (50 and 150 mg/kg), the non-selective NSAID tolmetin (TOL, 30 and 100 mg/kg) or the COX-2-selective NSAID celecoxib (CXIB, 20 and 60 mg/kg). Macroscopically visible and histologic lesions were evaluated. The ultrastructure of mucosal microvasculature was assessed.


RESULTS
(1) TOL and CXIB caused quantitatively greater endothelial damage and inflammatory cell infiltration than that induced by AMG; (2) AMG and CXIB, unlike TOL, did not cause epithelial damage after acute or chronic treatment, and (3) gastric lesions induced by TOL underwent adaptation during chronic treatment.


CONCLUSIONS
Endothelial cell damage in the gastric microvasculature is an early event following both non-selective and COX-2-selective inhibitors. The low gastric mucosal toxicity of AMG is confirmed after acute and chronic treatment.
Morini
Giuseppina
G
Department of Human Anatomy, Pharmacology and Forensic Medicine, University of Parma, Parma, Italy.
Guaita
Elena
E
Lazzaretti
Mirka
M
Grandi
Daniela
D
Coruzzi
Gabriella
G
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects*; D005998:Glycine / Q000031:analogs & derivatives* / Q000633:toxicity*; D008297:Male; D008854:Microscopy, Electron; D011758:Pyrroles / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011758:Pyrroles; C065762:ST 679; D005998:Glycine