Vilas-Boasa, V, Silva R, Nunes C, Reis S, Ferreira L, Vieira C, Carvalho F, de Bastos ML, Remiao F.
2013.
Mechanisms of P-gp inhibition and effects on membrane fluidity of a new rifampicin derivative, 1,8-dibenzoyl-rifampicin, JUL 18. TOXICOLOGY LETTERS. 220:259-266., Number 3
AbstractPurpose: To assess P-glycoprotein (P-gp)-modulation ability and the mechanisms of P-gp inhibition mediated by a new synthetic rifampicin derivative, 1,8-dibenzoyl-rifampicin (DiBenzRif), in an in vitro model of the blood-brain barrier (BBB), RBE4 cells, and in membrane mimetic models (liposomes). Methods: P-gp expression (western blot) and activity {[}rhodamine 123 accumulation studies] were assessed until 72 h of exposure to DiBenzRif. The effects on intracellular ATP levels and on P-gp ATPase activity were studied using luciferin-luciferase bioluminescence assay. Membrane fluidity changes were tracked by steady-state anisotropy measurements. Non-P-gp-related rhodamine 123 accumulation was evaluated using liposomes prepared with the main lipids present in RBE4 cell membranes. Results: A significant increase in intracellular rhodamine 123 content was observed in DiBenzRif-treated cells at all tested time-points. This effect was associated with a significant reduction in ATP intracellular levels, the inhibition of P-gp ATPase activity and a significant increase in membrane fluidity. DiBenzRif also favoured rhodamine 123 accumulation in a liposomal model of RBE4 cells, suggesting that it may be useful in increasing intracellular levels of substances that passively diffuse into the cells. Conclusion: DiBenzRif-induced inhibitory effect on P-gp increases xenobiotic accumulation in BBB cells, which may contribute to the development of therapeutic adjuvants to enhance brain penetration of drugs. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
Ferreira, PS, Nogueira TB, Costa VM, Branco PS, Ferreira LM, Fernandes E, Bastos ML, Meisel A, Carvalho F, Capela JP.
2013.
Neurotoxicity of ``ecstasy{''} and its metabolites in human dopaminergic differentiated SH-SY5Y cells, FEB 4. TOXICOLOGY LETTERS. 216:159-170., Number 2-3
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Gawande, MB, Rathi AK, Branco PS, Potewar TM, Velhinho A, Nogueira ID, Tolstogouzov A, Ghumman ACA, Teodoro OMND.
2013.
Nano-MgO-ZrO2 mixed metal oxides: characterization by SIMS and application in the reduction of carbonyl compounds and in multicomponent reactions. RSC ADVANCES. 3:3611-3617., Number 11
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