In vivo effects of amtolmetin guacyl on lipid peroxidation and antioxidant defence systems in different models of gastrointestinal injury.
1. The in vivo effects of the non-steroid anti-inflammatory drug (NSAID) amtolmetin guacyl (AMG) on lipid peroxidation (LP) and on antioxidant enzyme and non-enzyme defence systems were investigated in models of stomach and colon damages, induced by other NSAIDs, by ethanol or by 2,4,6-trinitrobenzenesulfonic acid (TNBS). 2. Indomethacin increased LP, glutathione peroxidase (GSH-PX) and glucose-6-phosphate dehydrogenase (Glu-6-P-DH) activities and decreased glutathione levels in gastric mucosa. Pretreatment with AMG normalized some of the parameters affected by indomethacin. 3. Treatment of rats with ethanol for 0.5 h led to a decrease in glutathione levels as well as activities of glutathione reductase and Glu-6-P-DH in gastric mucosa. AMG, administered 0.5 h before ethanol, limited the adverse actions of ethanol. 4. Amtolmetin guacyl failed to abolish the TNBS-induced changes in the followed-up parameters in colon mucosa and liver, but additional alterations (as with tolmetin) were not observed. 5. The beneficial profile of AMG in the various experimental models of free radical-induced damage investigated in this study suggests the possibility that this drug might possess antioxidant activity.
Kirkova
M
M
Institute of Physiology, Bulgarian Academy of Sciences, 23 Acad. G. Bonchev St, 1113 Sofia, Bulgaria.
Kesiova
M
M
Konstantinova
S
S
Alexandrova
A
A
Petrov
L
L
Tsvetanova
E
E
Todorov
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism*; D004195:Disease Models, Animal; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000473:pathology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007213:Indomethacin; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D011758:Pyrroles; C065762:ST 679; D000431:Ethanol; D005998:Glycine; D007213:Indomethacin