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

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.