Effects of
protizinic acid (PRT) on
prostaglandins (PG) and the production of
oxygen radicals were compared with those of other
non-steroidal anti-inflammatory agents.
Oral administration of 30 mg/kg of PRT,
indomethacin (IM), or
ibuprofen (IB) significantly inhibited
arachidonic acid-induced
erythema in guinea pigs. Although 30 mg/kg of PRT significantly inhibited PGE2-induced
erythema, IM and IB did not significantly inhibit it. PRT inhibited
phospholipase A2 (PLA2) activity, and the IC50 value was 2.1 X 10-4 M. On the other hand, IM and IB exerted no effect on the PLA2 activity at 3 X 10-4 M. These results suggest that PRT possesses a broader pharmacological activity on the PG system than IM and IB. As for effects on the production of
oxygen radicals, in order of relative inhibitory potency was PRT greater than
metiazinic acid (MA) = IM greater than IB =
phenylbutazone (PB) in the
xanthine oxidase assay, PB great than IM greater than PRT greater than MA = IB in the rabbit neutrophil
myeloperoxidase assay, and IM greater than PB greater than PRT greater than MA greater than IB in the guinea pig macrophage assay. In the rabbit neutrophil and aggregated
IgG-bound micropore filter assay, the order was PRT greater than MA greater than PB greater than IM = IB. Thus, the inhibitory effects of PRT was verified in all experiments on the production of
oxygen radicals in contrast to IB. In particular, it could be especially meaningful that PRT showed the most potent activity in the aggregated
IgG-bound micropore filter assay which has been reported to be a good model for studying the pathogenesis of inflammatory diseases believed to be caused by
immune complexes.