Oedematogenic activity induced by Kunitz-type inhibitors from Dimorphandra mollis seeds

Proteinase inhibitors from plants represent a form of storage protein or may be involved in plant defense mechanisms against pests and diseases. In this study, we have investigated the oedematogenic activity of DMTI (20 kDa) and DMTI-II (23 kDa), two serine proteinases inhibitors isolated from Dimor...

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Published in:Toxicon (Oxford) 2006-02, Vol.47 (2), p.150-155
Main Authors: Mello, Gláucia C., Desouza, Ivani A., Marangoni, Sérgio, Novello, José C., Antunes, Edson, Macedo, Maria Lígia R.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Dimorphandra mollis
Dose-Response Relationship, Drug
Edema - chemically induced
Fabaceae - chemistry
Inflammation
Kunitz family
Male
Medical sciences
Mimosoideae, trypsin inhibitor
N-terminal sequence
Plant poisons toxicology
Rats
Rats, Wistar
Seeds - chemistry
Time Factors
Toxicology
Trypsin Inhibitors - isolation & purification
Trypsin Inhibitors - pharmacology
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Summary:Proteinase inhibitors from plants represent a form of storage protein or may be involved in plant defense mechanisms against pests and diseases. In this study, we have investigated the oedematogenic activity of DMTI (20 kDa) and DMTI-II (23 kDa), two serine proteinases inhibitors isolated from Dimorphandra mollis (Leguminosae-Mimosoideae) seeds, belonging to the Kunitz family. Paw oedema was induced in male Wistar rats, and measured before and selected times after injection of the proteinase inhibitors. Injection of DMTI-II (3–100 μg/paw) induced a dose-dependent rat paw oedema of rapid onset and short duration, whereas DMTI (3–100 μg/paw) caused a discrete response. The histamine/5-HT receptor antagonist cyproheptadine (2 mg/kg) markedly reduced the DMTI-II-induced oedema. The bradykinin B 2 receptor antagonist JE 049 (0.6 mg/kg), the tachykinin NK 1 receptor antagonist SR140333 (100 μg/kg) or the NK 2 receptor antagonist SR48968 (1 mg/kg) all significantly reduced the DMTI-II-induced oedema. Depletion of sensory neuropeptides by capsaicin also resulted in a significant reduction of oedema formation. In rat isolated peritoneal mast cells, DMTI-II failed to directly release histamine. In conclusion, the proteinase inhibitor DMTI-II induces rat paw oedema by triggering the formation of different inflammatory mediators and pathways, where mast cells and sensory fibers seem to play a pivotal role.
ISSN:0041-0101
1879-3150
DOI:10.1016/j.toxicon.2005.10.003