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.