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 chromatography (GFC) on a Sephadex G-25 column. As a result, two bands which were characterized by the effects on hyaluronidase activity were obtained. The first band strongly activated the hyaluronidase, but a second band did not exhibit any effect on the enzyme activity. The first and second bands contained photoproducts with molecular weights (MW)>2700 and MW<728, respectively, determined by the GFC method. The photoproducts, 8-MOP-Spm-P(GFC) obtained from 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 than the second one in rats, differing from that induced by carrageenin. This photoproduct was a substance with lower cell toxicity because it did not cause hemolysis on red blood cells or the release of lactic dehydrogenase from mast cells in rats. The effects of various drugs on 8-MOP-Spm-P(GFC)-induced edema were investigated. As a result, edema formation was inhibited by drugs with an anti-histaminic action, such as alimemazine, dl-chlorpheniramine, promethazine, ketotifen and azelastine, and with anti-serotonin action such as cyproheptadine. On the other hand, tranilast did not show significant inhibition and indomethacin showed a tendency to increase its formation. These results suggested that 8-MOP-Spm-P(GFC) is a new inflammatory substance and is very useful as an agent to develop new anti-inflammatory drugs without cyclooxygenase inhibitory action.
Shigehara
N
N
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Miyataka
H
H
Kakegawa
H
H
Nishiki
M
M
Matsumoto
H
H
Isobe
A
A
Satoh
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced* / Q000188:drug therapy*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006461:Hemolysis / Q000187:drug effects; D006633:Histamine Antagonists / Q000494:pharmacology; D006821:Hyaluronoglucosaminidase / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008730:Methoxsalen / Q000737:chemistry / Q000633:toxicity*; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D013096:Spermine / Q000737:chemistry / Q000633:toxicity*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006633:Histamine Antagonists; D013096:Spermine; D007770:L-Lactate Dehydrogenase; D006821:Hyaluronoglucosaminidase; D008730:Methoxsalen