Human cells and cell membrane molecular models are affected in vitro by the nonsteroidal anti-inflammatory drug ibuprofen

Abstract

This report presents evidence that ibuprofen interacts with red cell membranes as follows: a) in scanning electron microscopy (SEM) studies on human erythrocytes induced shape changes at a concentration as low as 10μM; b) in isolated unsealed human erythrocyte membranes (IUM) induced mild increase in the water content or in their molecular dynamics at the hydrophobic-hydrophilic interphase, while a corresponding ordering decrease at the deep phospholipids acyl chain level; c) at physiological temperature (37°C), 300μM ibuprofen induced a significant increase in the generalized polarization (GP) of dimyristoylphosphatidylcholine (DMPC) large unilamellar vesicles (LUV), an indication that ibuprofen molecules locate in the head polar group region of DMPC; d) X-ray diffraction studies showed that ibuprofen concentrations≥300μM induced increasing structural perturbation to DMPC bilayers; e) differential scanning calorimetry (DSC) data showed that ibuprofen was able to alter the cooperativity of DMPC phase transition in a concentration-dependent manner, to destabilize the gel phase and that ibuprofen did not significantly perturb the organization of the lipid hydrocarbon chains. Additionally, the effect on the viability of both human promyelocytic leukemia HL-60 and human cervical carcinoma HeLa cells was studied.

Effect of Cholesterol on the Interaction of Cytochrome P450 Substrate Drug Chlorzoxazone with the Phosphatidylcholine Bilayer

“…These drugs also decreased the main transition temperature of DMPC bilayers and induced a broadening effect on the transition. 52 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 15 structure of CZX exhibits hydrophobic nature. This inference also agrees with the computer simulation result indicating that the location of CZX molecules in dioleoyl-PC bilayers is around the interface between the hydrophilic and hydrophobic parts of the bilayer membrane.…”

Non-steroidal anti-inflammatory drugs

“…31 Manrique-Moreno et al also analyzed the behavior of IBU in human erythrocytes and in red cell membrane models, combining DSC with other techniques such as X-ray diffraction and scanning electron microscopy. 33 Their experimental data suggested that this NSAID interacts with lipid bilayers and the erythrocyte membrane, affecting the morphology of the latter at concentrations lower than the therapeutic and toxic plasma levels. In particular, DSC experiments showed that IBU reduced the cooperativity between the PL molecules.…”

New Functions of Old Drugs: Aureolic Acid Group of Anti-Cancer Antibiotics and Non-Steroidal Anti-Inflammatory Drugs

“…These guide the microenvironment of the membrane interior and surface that in turn are expected to modulate the drug-membrane interaction. Ibuprofen interacts with red cell membranes and changes their shapes at a very low concentration (as low as 10 M) [148]. and other chemical groups (nimesulide, indomethacin, ibuprofen, etc.)…”