Inhibition of carrageenin-induced rat paw oedema by crotapotin, a polypeptide complexed with phospholipase A2

Autor: Gilberto De Nucci, José L. Donato, Stephen Hyslop, Giuseppe Cirino, Edson Antunes, Sergio Marangoni, Renato Faro, Benedito Oliveira, Elen C.T. Landucci
Přispěvatelé: E. C., Landucci, E., Antune, J. L., Donato, R., Faro, S., Hyslop, S., Marangoni, B., Oliveira, Cirino, Giuseppe, G. d., Nucci
Jazyk: angličtina
Rok vydání: 1995
Předmět:
Male
Platelet Aggregation
Administration
Oral
chemically induced/drug therapy
Guinea Pigs
Histamine Release
administration /&/ dosage/toxicity
Thromboxane B2
Pharmacology
Carrageenan
Histamine Release
Cell Degranulation
chemistry.chemical_compound
Wistar
Serotonin
drug effects
Humans
Injection
Edema
Mast Cells
Arachidonic Acid
biology
Intraperitoneal
Male
Mast Cell
Degranulation
Crotoxin
Thromboxane B2
Biochemistry
Arachidonic acid
pharmacology
Platelet Aggregation
Oral
Animals
Arachidonic Acid
pharmacology
Carrageenan
Injections
Intraperitoneal
Histamine
Research Article
Serotonin
metabolism
p-Methoxy-N-methylphenethylamine
Guinea Pigs
6-Ketoprostaglandin F1 alpha
drug effects
Crotoxin
Phospholipases A
administration /&/ dosage/toxicity
Cell Degranulation
administration /&/ dosage/toxicity
Phospholipase A2
Animals
Humans
p-Methoxy-N-methylphenethylamine
drug effects/physiology
Phospholipases A
Platelet Activating Factor
Rats
Wistar
metabolism
Phospholipases A2
Platelet Activating Factor
Animal
Edema
Platelet-activating factor
drug effects
Rats
Rat
metabolism
Administration
Rats
Disease Models
Animal
Phospholipases A2
chemistry
Eicosanoid
administration /&/ dosage/pharmacology/therapeutic use
Disease Model
biology.protein
Zdroj: Scopus-Elsevier
Popis: 1. The effect of purified crotapotin, a non-toxic non-enzymatic chaperon protein normally complexed to a phospholipase A2 (PLA2) in South America rattlesnake venom, was studied in the acute inflammatory response induced by carrageenin (1 mg/paw), compound 48/80 (3 micrograms/paw) and 5-hydroxytryptamine (5-HT) (3 micrograms/paw) in the rat hind-paw. The effects of crotapotin on platelet aggregation, mast cell degranulation and eicosanoid release from guinea-pig isolated lung were also investigated. 2. Subplantar co-injection of crotapotin (1 and 10 micrograms/paw) with carrageenin or injection of crotapotin (10 micrograms/paw) into the contralateral paw significantly inhibited the carrageenin-induced oedema. This inhibition was also observed when crotapotin (10-30 micrograms/paw) was administered either intraperitoneally or orally. Subplantar injection of heated crotapotin (15 min at 60 degrees C) failed to inhibit carrageenin-induced oedema. Subplantar injection of crotapotin (10 micrograms/paw) also significantly inhibited the rat paw oedema induced by compound 48/80, but it did not affect 5-HT-induced oedema. 3. In adrenalectomized animals, subplantar injection of crotapotin markedly inhibited the oedema induced by carrageenin. The inhibitory effect of crotapotin was also observed in rats depleted of histamine and 5-HT stores. 4. Crotapotin (30 micrograms/paw) had no effect on either the histamine release induced by compound 48/80 in vitro or on the platelet aggregation induced by both arachidonic acid (1 nM) and platelet activating factor (1 microM) in human platelet-rich plasma. The platelet aggregation and thromboxane B2 (TXB2) release induced by thrombin (100 mu ml-1) in washed human platelets were also not affected by crotapotin. In addition, crotapotin (10 microg/paw) did not affect the release of 6-oxo-prostaglandin Fla, and TXB2 induced by ovalbumin in sensitized guinea-pig isolated lungs.5. Our results indicate that the anti-inflammatory activity of crotapotin is not due to endogenous corticosteroid release or inhibition of cyclo-oxygenase activity. It is possible that crotapotin may interact with extracellular PLA2 generated during the inflammatory process thereby reducing its hydrolytic activity.
Databáze: OpenAIRE
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