Can NO-indomethacin counteract the topical gastric toxicity induced by indomethacin interactions with phospholipid bilayers?
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.
Palavras-chave
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