Antiinflammatory effect of a protein kinase C inhibitor (K-252a) on the development of the dextran-induced paw edema in the rat (preliminary results).
The effect of a metabolite of Nocardiopsis sp. as a protein kinase C inhibitor from microbial origin was investigated on the onset and development of dextran-induced paw edema in the rat. It was published that this compound (K-252a) interferes with histamine release from mast cells, while dextran-induced paw and nose edema are induced by vasoactive agents, like histamine etc., released from the disrupted mast cells. The antiinflammatory effect of the K-252a is effectuated by the inhibition of protein kinase C. Groups of male Wistar rats with 180-200 g b.w. were used; each group consisted of 10-10 rats. The following groups were consisted: rats given orally DMSO (control), rats given 1 mg/kg, or 3 mg/kg b.w. of K-252a dissolved in DMSO and given p.o. one hour before dextran injection. Dextran (BDH Chem. LTD, molW: 200.000, England) was injected intraperitoneally in 10% solution, in a dose of one ml/100 g b.w. Volume of the hind leg was measured by a mercury plethysmometer. Time-sequence of the edema was followed. Increase in volume of hind leg paw was related to its 0-min volume in %. Results were analyzed by the Kruskal-Wallis-test. Edema of the legs and noses appeared in each of the control rats in one hour. The 1 mg/kg dose of K-252a retarded the appearance of the edema by 1 hour, the 3 mg/kg dose, however, prevented its onset for 4 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
Papp
M
M
Institute of Experimental Medicine of the Hungarian Academy of Sciences, Budapest.
Kase
H
H
Gigler
G
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D003911:Dextrans; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005528:Foot / Q000473:pathology; D006614:Hindlimb / Q000473:pathology; D026121:Indole Alkaloids; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D003911:Dextrans; D026121:Indole Alkaloids; C049985:staurosporine aglycone; D011493:Protein Kinase C