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Can NO-indomethacin counteract the topical gastric toxicity induced by indomethacin interactions with phospholipid bilayers?
Pereira-Leite, Catarina; Nunes, Cláudia; Bozelli, José C; Schreier, Shirley; Kamma-Lorger, Christina S; Cuccovia, Iolanda M; Reis, Salette.
Afiliação
  • Pereira-Leite C; LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, 05508-000 São Paulo, Brazil.
  • Nunes C; LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
  • Bozelli JC; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, 05508-000 São Paulo, Brazil; Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S4L8, Canada.
  • Schreier S; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, 05508-000 São Paulo, Brazil.
  • Kamma-Lorger CS; ALBA Synchrotron, Consorcio para la Construcción, Equipamiento y Explotación del Laboratorio de Luz de Sincrotrón (CELLS), Carrer de la Llum 2-26, 08290 Cerdanyola del Vallès, Barcelona, Spain.
  • Cuccovia IM; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, 05508-000 São Paulo, Brazil. Electronic address: imcuccov@iq.usp.br.
  • Reis S; LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. Electronic address: shreis@ff.up.pt.
Colloids Surf B Biointerfaces ; 169: 375-383, 2018 09 01.
Article em En | MEDLINE | ID: mdl-29803153
Nitric oxide (NO)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) have been developed to overcome the gastrointestinal and cardiovascular toxicity of NSAIDs, by chemically associating a NO-releasing moiety with commercial NSAIDs. Since increasing evidence supports that NSAIDs toxicity is related to their topical actions in membrane lipids, this work aims to evaluate the impact of adding a NO-releasing moiety to parent NSAIDs regarding their effect on lipid bilayers. Thus, the interactions of NO-indomethacin and indomethacin (parent drug) with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers were described herein at pH 3.0 and 7.4. Diverse experimental techniques were combined to characterize the partitioning and location of drugs in DMPC bilayers, and to analyze their effect on the lipid phase transition and the bilayer structure and dynamics. The partitioning of NO-indomethacin into DMPC bilayers was similar to that of charged indomethacin and smaller than that of neutral indomethacin. Both drugs were found to insert the DMPC bilayer and the membrane location of indomethacin was pH-dependent. NO-indomethacin and indomethacin induced a decrease of the main phase transition temperature of DMPC. The effect of these drugs on the bilayer structure and dynamics was dependent on diverse factors, namely drug ionization state, drug:lipid molar ratio, temperature and lipid phase. It is noteworthy that NO-indomethacin induced more pronounced alterations in the biophysical properties of DMPC bilayers than indomethacin, considering equivalent membrane concentrations. Such modifications may have in vivo implications, particularly in the gastric mucosa, where NO-NSAIDs-induced changes in the protective properties of phospholipid layers may contribute to the occurrence of adverse effects.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipídeos / Indometacina / Mucosa Gástrica / Bicamadas Lipídicas / Óxido Nítrico Limite: Humans Idioma: En Revista: Colloids Surf B Biointerfaces Assunto da revista: QUIMICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipídeos / Indometacina / Mucosa Gástrica / Bicamadas Lipídicas / Óxido Nítrico Limite: Humans Idioma: En Revista: Colloids Surf B Biointerfaces Assunto da revista: QUIMICA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda