title: The bradykinin B1 receptor antagonist R-954 inhibits Ehrlich tumor growth in rodents.
abstract: The present study investigated the effects of a new bradykinin B(1) receptor antagonist, R-954, on the development of Ehrlich ascitic tumor (EAT) induced by the intraperitoneal inoculation of EAT cells in mice and the formation of a solid tumor by the subcutaneous injection of the cells in rat paw. The development of the tumor was associated with an increase in mouse total cell counts in bone marrow (10.8-fold), ascitic fluid (14.6-fold), and blood (12.6-fold). R-954 (2mg/kg, s.c.) significantly reduced the ascitic fluid volume (63.7%) and the mouse weight gain (30.5%) after 10 consecutive days of treatment. The B(1) antagonist as well as the anti-neoplasic drug vincristine also significantly inhibited the increase in total cell count in bone marrow, ascitic fluid, and blood. R-954 reduced significantly the total protein extravasation (57.3%), the production of nitric oxide (56%), PGE(2) production (82%), and TNFα release (85.7%) in mice peritoneal cavity whereas vincristine reduced the release of these inflammatory mediators by 84-94%. The increase in paw edema after intraplantar injection of EAT cells was reduced by approximately 52% by either R-954 or vincristine treatment. In conclusion, this study presents for the first time the antitumoral activity of a new bradykinin B(1) receptor antagonist on ascitic and solid tumors induced by Ehrlich cell inoculation in mice and rats.
authors.affiliation: Laboratório de Farmacologia da Inflamação e do Óxido Nítrico, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373. Prédio do CCS, bloco J, sala 10, Rio de Janeiro, Brazil.
authors.forename: Patricia Dias
authors.initials: PD
authors.lastname: Fernandes
authors.forename: Niele de Matos
authors.initials: Nde M
authors.lastname: Gomes
authors.forename: Pierre
authors.initials: P
authors.lastname: Sirois
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001202:Ascitic Fluid / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001772:Blood Cell Count; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
chemical_list: C476306:Ac-Orn-(Oic2, alpha-MePhe5, D-betaNal7, Ile8)desArg9-bradykinin; D000970:Antineoplastic Agents; D065169:Bradykinin B1 Receptor Antagonists; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D014750:Vincristine; D015232:Dinoprostone; D001920:Bradykinin