PRO-INFLAMMATORY ACTIVITY INDUCED BY A KUNITZ-TYPE INHIBITOR FROM Dimorphandra mollis SEEDS

DE MELLO G.C. (1), DE SOUZA I.A. (1), MACEDO M.L.R. (2,3), ANTUNES E. (1)

(1) Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas/SP, Brazil; (2) LPPFB, Department of Biological Sciences and the Health/UFMS – Três Lagoas/MS; (3) Department of Biochemistry, Institute of Biology, UNICAMP, Campinas/SP, Brazil.

Plant proteinase inhibitors have been described as useful tools in biochemical and physiological studies to understand the proteinase functions in human pathologies, e.g., hemorrhage, inflammation and cancer. In a recent study, we have investigated the oedematogenic activity of DMTI-II (20 kDa), a serine proteinase inhibitor Kunitz-type isolated from D. mollis (Leguminosae-Mimosoideae) seeds. Injection of DMTI-II (3–100 mg/paw) induced a dose-dependent rat paw oedema of rapid onset and short duration, where mast cells and sensory fibers seem to play a pivotal role (1). Since this proteinase inhibitor is known to present inflammatory activity, this study aimed to investigate the leukocyte migration induced by DMTI-II. Male Wistar rats (180-200g) were intraperitoneally injected with DMTI-II (3-30 mg/cavity). Four and sixteen h thereafter the total and differential leukocyte counts were performed in peritoneal lavage fluid. DMTI-II (10 mg/cavity) induced significant total leukocyte accumulation at 4 and 16 h after injection. Neutrophil and eosinophil counts were increased at 4 h (16 and 14-fold increase, respectively), reaching a maximum response at 16 h (22 and 17-fold increase, respectively). The presence of early eosinophils starting from 4 h is not a common event in the experimental models of the inflammatory response. Further investigation is necessary to elucidate the mechanism of DMTI-II action as well as the inflammatory mediators involved.

KEY WORDS: Dimorphandra mollis, Kunitz-type inhibitors, inflammatory activity

REFERENCE: 1. Mello, G.C. et al. Oedematogenic activity induced by Kunitz-type inhibitors from Dimorphandra mollis seeds. Toxicon, 2006, 47: 150-155.

FINANCIAL SUPPORT: CAPES and CNPq

CORRESPONDENCE TO: GLÁUCIA C MELLO, Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, SP, Brazil. Postal Code 6111; CEP 13084 973. Email: glaumello@terra.com.br