title: The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models.
abstract: The Bauhinia bauhinioides Kallikrein Inhibitor (BbKI) is a Kunitz-type serine peptidase inhibitor of plant origin that has been shown to impair the viability of some tumor cells and to feature a potent inhibitory activity against human and rat plasma kallikrein (Kiapp 2.4 nmol/L and 5.2 nmol/L, respectively). This inhibitory activity is possibly responsible for an effect on hemostasis by prolonging activated partial thromboplastin time (aPTT). Because the association between cancer and thrombosis is well established, we evaluated the possible antithrombotic activity of this protein in venous and arterial thrombosis models. Vein thrombosis was studied in the vena cava ligature model in Wistar rats, and arterial thrombosis in the photochemical induced endothelium lesion model in the carotid artery of C57 black 6 mice. BbKI at a concentration of 2.0 mg/kg reduced the venous thrombus weight by 65% in treated rats in comparison to rats in the control group. The inhibitor prolonged the time for total artery occlusion in the carotid artery model mice indicating that this potent plasma kallikrein inhibitor prevented thrombosis.
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, Rua três de Maio, 100, 04044-020 São Paulo, Brazil.
authors.forename: Marlon V
authors.initials: MV
authors.lastname: Brito
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, Rua três de Maio, 100, 04044-020 São Paulo, Brazil.
authors.forename: Cleide
authors.initials: C
authors.lastname: de Oliveira
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, Rua três de Maio, 100, 04044-020 São Paulo, Brazil.
authors.forename: Bruno R
authors.initials: BR
authors.lastname: Salu
authors.affiliation: Laboratório de Bioquímica e Biofísica, Instituto Butantan, Av Vital Brazil, 1500, 05503-900 São Paulo, Brazil.
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Andrade
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, Rua três de Maio, 100, 04044-020 São Paulo, Brazil.
authors.forename: Paula M D
authors.initials: PM
authors.lastname: Malloy
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, Rua três de Maio, 100, 04044-020 São Paulo, Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Sato
authors.affiliation: Universidade Estadual de Campinas, Instituto de Biologia, Rua Charles Darwin, s/n, 13083-863 Campinas, Brazil.
authors.forename: Cristina P
authors.initials: CP
authors.lastname: Vicente
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, Rua três de Maio, 100, 04044-020 São Paulo, Brazil.
authors.forename: Misako U
authors.initials: MU
authors.lastname: Sampaio
authors.affiliation: Departamento de Cirurgia e Ortopedia, Faculdade de Medicina de Botucatu, UNESP, 18618-970, Botucatu, Brazil. Electronic address: fhmaffei@uol.com.br.
authors.forename: Francisco H A
authors.initials: FH
authors.lastname: Maffei
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, Rua três de Maio, 100, 04044-020 São Paulo, Brazil. Electronic address: olivaml.bioq@epm.br.
authors.forename: Maria Luiza V
authors.initials: ML
authors.lastname: Oliva
mesh_terms: D000818:Animals; D036481:Bauhinia; D001777:Blood Coagulation / Q000187:drug effects; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D010940:Plant Proteins / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*
chemical_list: C434623:BbKI protein, Bauhinia bauhinioides; D005343:Fibrinolytic Agents; D010940:Plant Proteins; D013917:Thrombin
keywords: Blood coagulation; Kallikrein; Kunitz inhibitor; Thrombosis; Trypsin inhibitor; Tumor cells