Lucinéia Reuse Albiero1,2, Micássio Fernandes de Andrade3,4, Larissa Fávaro Marchi5, Ana Paula Landi-Librandi5, Andréa Silva Garcia de Figueiredo-Rinhel5, Camila Andressa Carvalho5, Luciana Mariko Kabeya5, Renê Donizeti Ribeiro de Oliveira6, Ana Elisa Caleiro Seixas Azzolini5, Mônica Tallarico Pupo7, Flávio da Silva Emery7, Yara Maria Lucisano-Valim8. 1. Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Ribeirão Preto, SP, 14049-900, Brazil. lucineia_albiero@hotmail.com. 2. Federal University of Mato Grosso, Sinop, MT, Brazil. lucineia_albiero@hotmail.com. 3. Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Ribeirão Preto, SP, 14049-900, Brazil. micassiofernandes@gmail.com. 4. School of Health Sciences, The State University of Rio Grande do Norte, Mossoró, RN, Brazil. micassiofernandes@gmail.com. 5. Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/n, Ribeirão Preto, SP, 14040-903, Brazil. 6. Division of Rheumatology, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Ribeirão Preto, SP, 14049-900, Brazil. 7. Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/n, Ribeirão Preto, SP, 14040-903, Brazil. 8. Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/n, Ribeirão Preto, SP, 14040-903, Brazil. yaluva@usp.br.
Abstract
OBJECTIVE: To examine whether free (3-PD-5free) and/or liposomal (3-PD-5lipo) 6,7-dihydroxy-3-[3',4'-methylenedioxyphenyl]-coumarin (3-PD-5) (1) modulate the effector functions of neutrophils from patients with rheumatoid arthritis under remission (i-RA) and with active disease (a-RA), in vitro; and (2) exert anti-inflammatory effect in a rat model of zymosan-induced acute joint inflammation. METHODS AND RESULTS: Incorporation of 3-PD-5 into unilamellar liposomes of soya phosphatidylcholine and cholesterol was efficient (57.5 ± 7.9%) and yielded vesicles with low diameter (133.7 ± 18.4 nm), polydispersity index (0.39 ± 0.06), and zeta potential (- 1.22 ± 0.34 mV). 3-PD-5free (1 µM) and 3-PD-5lipo (3 µM) equally suppressed elastase release and reactive oxygen species generation in neutrophils from healthy subjects and i-RA and a-RA patients, stimulated with immune complexes. 3-PD-5free (20 µM) suppressed the release of neutrophil extracellular traps and chemotaxis in vitro, without clear signs of cytotoxicity. 3-PD-5lipo (1.5 mg/kg, i.p.) diminished joint edema and synovial infiltration of total leukocytes and neutrophils, without changing the synovial levels of TNF-α, IL-1β, and IL-6. CONCLUSION: Altogether, the results reported herein indicate that 3-PD-5 is a promising modulator of the early stages of acute joint inflammation that can help to diminish not only excessive neutrophil infiltration in the synovia but also neutrophil activation and its outcomes in RA patients.
OBJECTIVE: To examine whether free (3-PD-5free) and/or liposomal (3-PD-5lipo) 6,7-dihydroxy-3-[3',4'-methylenedioxyphenyl]-coumarin (3-PD-5) (1) modulate the effector functions of neutrophils from patients with rheumatoid arthritis under remission (i-RA) and with active disease (a-RA), in vitro; and (2) exert anti-inflammatory effect in a rat model of zymosan-induced acute joint inflammation. METHODS AND RESULTS: Incorporation of 3-PD-5 into unilamellar liposomes of soya phosphatidylcholine and cholesterol was efficient (57.5 ± 7.9%) and yielded vesicles with low diameter (133.7 ± 18.4 nm), polydispersity index (0.39 ± 0.06), and zeta potential (- 1.22 ± 0.34 mV). 3-PD-5free (1 µM) and 3-PD-5lipo (3 µM) equally suppressed elastase release and reactive oxygen species generation in neutrophils from healthy subjects and i-RA and a-RA patients, stimulated with immune complexes. 3-PD-5free (20 µM) suppressed the release of neutrophil extracellular traps and chemotaxis in vitro, without clear signs of cytotoxicity. 3-PD-5lipo (1.5 mg/kg, i.p.) diminished joint edema and synovial infiltration of total leukocytes and neutrophils, without changing the synovial levels of TNF-α, IL-1β, and IL-6. CONCLUSION: Altogether, the results reported herein indicate that 3-PD-5 is a promising modulator of the early stages of acute joint inflammation that can help to diminish not only excessive neutrophil infiltration in the synovia but also neutrophil activation and its outcomes in RA patients.
Authors: Jolanda M van den Hoven; Sophie R Van Tomme; Josbert M Metselaar; Bastiaan Nuijen; Jos H Beijnen; Gert Storm Journal: Mol Pharm Date: 2011-06-17 Impact factor: 4.939
Authors: Ana Paula Landi-Librandi; Carlos Alberto de Oliveira; Ana Elisa Caleiro Seixas Azzolini; Luciana Mariko Kabeya; José Orestes Del Ciampo; Maria Vitória Lopes Badra Bentley; Yara Maria Lucisano-Valim Journal: J Microencapsul Date: 2011 Impact factor: 3.142
Authors: Hidenori Hattori; Kulandayan K Subramanian; Jiro Sakai; Yonghui Jia; Yitang Li; Timothy F Porter; Fabien Loison; Bara Sarraj; Anongnard Kasorn; Hakryul Jo; Catlyn Blanchard; Dorothy Zirkle; Douglas McDonald; Sung-Yun Pai; Charles N Serhan; Hongbo R Luo Journal: Proc Natl Acad Sci U S A Date: 2010-02-08 Impact factor: 11.205
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