title: Anti-allergic effects of nilotinib on mast cell-mediated anaphylaxis like reactions.
abstract: Nilotinib is a new orally bioavailable potent tyrosine kinase inhibitor that is used for the treatment of BCR-ABL-positive chronic myelogenous leukemia. However, its effect on mast cell-mediated anaphylactic reaction is still not known. The present study aimed to investigate the effect of nilotinib on the anaphylactic allergic reaction and study its possible mechanism(s) of action. Nilotinib administration prevented systemic anaphylaxis in mice, mediated by compound 48/80, in a dose- and time-dependent manner. Also, nilotinib significantly inhibited (P<0.05) allergic paw edema in rats. Furthermore, nilotinib significantly decreased (P<0.05) the IgE-mediated passive cutaneous anaphylaxis in a dose dependent manner. In addition, nilotinib dose-dependently reduced histamine release from the rat peritoneal mast cells activated either by compound 48/80 or by ovalbumin. Moreover, nilotinib attenuated the secretion of pro-inflammatory cytokine, tumor necrosis factor (TNF)-α expression in the rat peritoneal mast cells. These findings provide evidence that nilotinib inhibits mast cell-derived immediate-type allergic reactions and so it could be a candidate as an anti-allergic agent.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. dinaagamy1@yahoo.com
authors.forename: Dina S
authors.initials: DS
authors.lastname: El-Agamy
mesh_terms: D000707:Anaphylaxis / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004487:Edema / Q000188:drug therapy / Q000276:immunology; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D018926:Anti-Allergic Agents; D016207:Cytokines; D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D003189:p-Methoxy-N-methylphenethylamine; D010047:Ovalbumin; D011505:Protein-Tyrosine Kinases; C498826:nilotinib