Inflammatory action of 8-methoxypsoralen-spermine photoproduct (8-MOP-Spm-P-GFC) and effects of various drugs on rat paw edema induced by 8-MOP-Spm-P-GFC
N. Shigehara et al., Inflammatory action of 8-methoxypsoralen-spermine photoproduct (8-MOP-Spm-P-GFC) and effects of various drugs on rat paw edema induced by 8-MOP-Spm-P-GFC, BIOL PHAR B, 22(11), 1999, pp. 1202-1206
The photoproducts produced by irradiating 8-methoxypsoralen (8-MOP) in the
presence of spermine (Spm) were fractionated using gel filtration chromatog
raphy (GFC) on a Sephadex G25 column. As a result, two bands which were cha
racterized by the effects on hyaluronidase activity were obtained. The firs
t band strongly activated the hyaluronidase, but a second band did not exhi
bit any effect on the enzyme activity. The first and second bands contained
photoproducts with molecular weights (MW)>2700 and MW<728, respectively, d
etermined by the GFC method. The photoproducts, 8-MOP-Spm-P-GFC obtained fr
om the first band, but not the photoproducts with lower MW from the second
band, showed enzyme activating action.
8-MOP-Spm-P-GFC induced paw edema, which was stronger in the first phase th
an the second one in rats, differing from that induced by carrageenin, This
photoproduct was a substance with lower cell toxicity because it did not c
ause hemolysis on red blood cells or the release of lactic dehydrogenase fr
om mast cells in rats.
The effects of various drugs on 8-MOP-Spm-P-GFC-induced edema were investig
ated. As a result, edema formation was inhibited by drugs with an anti-hist
aminic action, such as alimemazine, dl-chlorpheniramine, promethazine, keto
tifen and azelastine, and with anti-serotonin action such as cyproheptadine
. On the other hand, tranilast did not show significant inhibition and indo
methacin showed a tendency to increase its formation.
These results suggested that 8-MOP-Spm-P-GFC is a new inflammatory substanc
e and is very useful as an agent to develop new anti-inflammatory drugs wit
hout cyclooxygenase inhibitory action.