Effect of anti-inflammatory drugs on splenocyte membrane fluidity.
In this study, fluorescence anisotropy measurements were performed using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene to investigate the effects on membrane fluidity resulting from the interaction between nonsteroidal anti-inflammatory drugs (NSAIDs)-indomethacin, diclofenac, piroxicam, tenoxicam, indoprofen, clonixin, and etodolac-and mouse splenocyte membranes. This study was performed in splenocyte membranes because most of the fluidity studies have been performed in membrane models; thus, clear correlations of the pharmacological action of drugs with molecular effects at the cellular membrane level were lacking. Besides providing a basis for studying the molecular mechanism of pharmacological action of NSAIDs, this research provides a data analysis of steady-state anisotropy measurements, taking into account that the probe itself strongly influences the data given that this problem is usually overlooked. Results show that the anti-inflammatory drugs indomethacin, diclofenac, piroxicam, and tenoxicam increase the membrane fluidity in a concentration-dependent manner. Their order of effectiveness reflected in their respective IC50 values (concentration of each NSAID required to increase the fluidizing effect ratio by 50%) is as follows: tenoxicam>piroxicam>indomethacin>clonixin. For the other drugs, the perturbation in membrane fluidity is not evident under these circumstances.
Ferreira
Helena
H
REQUIMTE, Departamento de Química-Física, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4050-047 Porto, Portugal.
Lúcio
Marlene
M
Lima
José L F C
JL
Cordeiro-da-Silva
Anabela
A
Tavares
Joana
J
Reis
Salette
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D008560:Membrane Fluidity; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D005456:Fluorescent Dyes