Differential effects of Mandevilla velutina compounds on paw oedema induced by phospholipase A2 and phospholipase C.
This study compares the effect of Mandevilla velutina compounds with some anti-inflammatory drugs against phospholipase A2- and phospholipase C-induced rat hindpaw oedema. Injection of phospholipase A2 (Naja naja, 2.5-20 U/paw) and phospholipase C (Clostridium perfringens, 0.03-0.05 U/paw) caused a dose-and-time-related increase in paw oedema. Compounds MV 8608 (55 mumol/kg) and MV 8612 (32 mumol/kg, i.p.) inhibited phospholipase A2-induced paw oedema without interfering with phospholipase C-induced oedema. Local injection of both M. velutina compounds also partially attenuated the oedema evoked by phospholipases A2 and C. Dexamethasone (1.3 mumol/kg, p.o.) suppressed only phospholipase A2-induced paw oedema, while indomethacin (11 mumol/kg, p.o.) attenuated only the early phase of phospholipase C-induced oedema. By contrast, phenidone (616 mumol/kg, i.p.) inhibited only phospholipase C-induced oedema, while cyproheptadine (31 mumol/kg) and pyrilamine (100 mumol/kg, p.o.) inhibited only phospholipase A2 oedema. Treatment of animals with compound 48/80 markedly suppressed phospholipase A2-induced paw oedema and to a lesser degree the oedema caused by phospholipase C. Our results indicate that there are marked differences regarding the mechanisms underlying the paw oedema responses caused by phospholipase A2 and phospholipase C. In addition, our data show that M. velutina compounds cause potent and long-lasting inhibition of the pro-inflammatory action of phospholipase A2, an effect which may account for their reported anti-inflammatory activities.
Neves
P C
PC
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Neves
M C
MC
Cruz
A B
AB
Sant'Ana
A E
AE
Yunes
R A
RA
Calixto
J B
JB
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001920:Bradykinin / Q000037:antagonists & inhibitors; D003533:Cyproheptadine / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D006027:Glycosides / Q000302:isolation & purification / Q000627:therapeutic use*; D008297:Male; D010741:Phospholipases A; D054467:Phospholipases A2; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D013256:Steroids / Q000302:isolation & purification / Q000627:therapeutic use*; D010738:Type C Phospholipases
D000893:Anti-Inflammatory Agents; D006027:Glycosides; D013256:Steroids; C085133:MV 8608; C085132:MV 8612; D003533:Cyproheptadine; D003907:Dexamethasone; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D001920:Bradykinin