Gastric anti-ulcerative and anti-inflammatory activity of metyrosine in rats.
In this study, the anti-inflammatory and anti-ulcerative effects of metyrosine, a selective tyrosine hydroxylase enzyme inhibitor, were investigated in rats. For ulcer experiments, indomethacin-induced gastric ulcer tests and ethanol-induced gastric ulcer tests were used. For these experiments, rats were fasted for 24 h. Different doses of metyrosine and 25 mg/kg doses of ranitidine were administered to rats, followed by indomethacin at 25 mg/kg for the indomethacin-induced ulcer test, or 50% ethanol for the ethanol-induced test. Results have shown that at all of the doses used (50, 100 and 200 mg/kg), metyrosine had significant anti-ulcerative effects in both indomethacin and ethanol-induced ulcer tests. Metyrosine doses of 100 and 200 mg/kg (especially the 200 mg/kg dose) also inhibited carrageenan-induced paw inflammation even more effectively than indomethacin. In addition, to characterize the anti-inflammatory mechanism of metyrosine we investigated its effects on cyclooxygenase (COX) activity in inflammatory tissue (rat paw). The results showed that all doses of metyrosine significantly inhibited high COX-2 activity. The degree of COX-2 inhibition correlated with the increase in anti-inflammatory activity. In conclusion, we found that metyrosine has more anti-inflammatory effects than indomethacin and that these effects can be attributed to the selective inhibition of COX-2 enzymes by metyrosine. We also found that adrenalin levels are reduced upon metyrosine treatment, which may be the cause of the observed gastro-protective effects of this compound.
Albayrak
Abdulmecit
A
Department of Pharmacology, Faculty of Pharmacy, Ataturk University, 25240 Erzurum, Turkey.
Polat
Beyzagul
B
Cadirci
Elif
E
Hacimuftuoglu
Ahmet
A
Halici
Zekai
Z
Gulapoglu
Mine
M
Albayrak
Fatih
F
Suleyman
Halis
H
D000818:Animals; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004487:Edema / Q000473:pathology; D000431:Ethanol; D005528:Foot / Q000473:pathology; D005753:Gastric Mucosa / Q000473:pathology; D007213:Indomethacin; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000473:pathology / Q000517:prevention & control*; D019805:alpha-Methyltyrosine / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D000431:Ethanol; D019805:alpha-Methyltyrosine; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin