title: Mast cells and histamine play an important role in edema and leukocyte recruitment induced by Potamotrygon motoro stingray venom in mice.
abstract: This work aimed to investigate mechanisms underlying the inflammatory response caused by Potamotrygon motoro stingray venom (PmV) in mouse paws. Pre-treatment of animals with a mast cell degranulation inhibitor (cromolyn) diminished edema (62% of inhibition) and leukocyte influx into the site of PmV injection. Promethazine (histamine type 1 receptor antagonist) or thioperamide (histamine type 3 and 4 receptor antagonist) also decreased edema (up to 30%) and leukocyte numbers, mainly neutrophils (40-50 %). Cimetidine (histamine type 2 receptor antagonist) had no effect on PmV-induced inflammation. In the RBL-2H3 lineage of mast cells, PmV caused proper cell activation, in a dose-dependent manner, with release of PGD2 and PGE2. In addition, the role of COXs products on PmV inflammatory response was evaluated. Indomethacin (COX-1/COX-2 inhibitor) or etoricoxib (COX-2 inhibitor) partially diminished edema (around 20%) in PmV-injected mice. Indomethacin, but not etoricoxib, modulated neutrophil influx into the site of venom injection. In conclusion, mast cell degranulation and histamine, besides COXs products, play an important role in PmV-induced reaction. Since PmV mechanism of action remains unknown, hindering accurate treatment, clinical studies can be performed to validate the prescription of antihistaminic drugs, besides NSAIDs, to patients injured by freshwater stingrays.
authors.affiliation: Laboratory of Immunopathology, Butantan Institute, Av. Vital Brasil 1500, 05503-900, São Paulo, SP, Brazil.
authors.forename: Louise F
authors.initials: LF
authors.lastname: Kimura
authors.affiliation: Laboratory of Immunopathology, Butantan Institute, Av. Vital Brasil 1500, 05503-900, São Paulo, SP, Brazil.
authors.forename: José Pedro
authors.initials: JP
authors.lastname: Prezotto-Neto
authors.affiliation: Laboratory of Immunopathology, Butantan Institute, Av. Vital Brasil 1500, 05503-900, São Paulo, SP, Brazil.
authors.forename: Bianca C L F
authors.initials: BC
authors.lastname: Távora
authors.affiliation: Laboratory of Immunopathology, Butantan Institute, Av. Vital Brasil 1500, 05503-900, São Paulo, SP, Brazil.
authors.forename: Eliana L
authors.initials: EL
authors.lastname: Faquim-Mauro
authors.affiliation: Laboratory of Immunopathology, Butantan Institute, Av. Vital Brasil 1500, 05503-900, São Paulo, SP, Brazil.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Pereira
authors.affiliation: Laboratory of Cell Biology, Butantan Institute, Av. Vital Brasil 1500, 05503-900, São Paulo, SP, Brazil.
authors.forename: Marta M
authors.initials: MM
authors.lastname: Antoniazzi
authors.affiliation: Laboratory of Cell Biology, Butantan Institute, Av. Vital Brasil 1500, 05503-900, São Paulo, SP, Brazil.
authors.forename: Simone G S
authors.initials: SG
authors.lastname: Jared
authors.affiliation: Laboratory of Pharmacology, Butantan Institute, Av. Vital Brasil 1500, 05503-900, São Paulo, SP, Brazil.
authors.forename: Catarina F P
authors.initials: CF
authors.lastname: Teixeira
authors.affiliation: Laboratory of Pathophysiology, Butantan Institute, Av. Vital Brasil 1500, 05503-900, São Paulo, SP, Brazil.
authors.forename: Marcelo L
authors.initials: ML
authors.lastname: Santoro
authors.affiliation: Laboratory of Immunopathology, Butantan Institute, Av. Vital Brasil 1500, 05503-900, São Paulo, SP, Brazil. Electronic address: katia.barbaro@butantan.gov.br.
authors.forename: Katia C
authors.initials: KC
authors.lastname: Barbaro
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000473:pathology*; D018940:Elasmobranchii / Q000378:metabolism*; D000077613:Etoricoxib; D005397:Fish Venoms / Q000633:toxicity*; D006632:Histamine / Q000633:toxicity*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D011398:Promethazine / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013450:Sulfones / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D005397:Fish Venoms; D006634:Histamine H1 Antagonists; D008565:Membrane Proteins; D011725:Pyridines; D013450:Sulfones; D006632:Histamine; D051545:Cyclooxygenase 1; C496512:Ptgs1 protein, mouse; D011398:Promethazine; D015232:Dinoprostone; D015230:Prostaglandin D2; D000077613:Etoricoxib
keywords: Ciclooxygenases; Histamine; Inflammatory response; Mast cell; Stingray venom