Correlation between fluidising effects on phospholipid membranes and mitochondrial respiration of propofol and p-nitrosophenol homologues.
Nitrosopropofol (2-6-diisopropyl-4-nitrosophenol) has dramatic consequences for respiration, ATP synthesis and the transmembrane potential of isolated rat liver mitochondria at concentrations at which propofol (2-6-diisopropylphenol) does not cause any apparent effects. These results correlate well with the observation that nitrosopropofol is also a stronger perturbing agent of phospholipid membranes. In this paper we verify the possible biological activity of different phenols and nitrosophenols on mitochondrial respiration. We then discuss their interactions with phospholipid liposomes, studied with differential scanning calorimetry, spin labelling techniques and UV-Vis spectrophotometry, in order to obtain information on drug distribution and the modifications they impose on lipid bilayer. The results of the experiments performed on mitochondria and model membranes prove an interesting correlation between the effects of the molecules on both systems.
Momo
Federico
F
Department of Physical Chemistry, University of Venice, Dorsoduro 2137, 30123 Venice, Italy. momo@unive.it
Fabris
Sabrina
S
Wisniewska
Anna
A
Fiore
Cristina
C
Bindoli
Alberto
A
Scutari
Guido
G
Stevanato
Roberto
R
D000818:Animals; D002152:Calorimetry, Differential Scanning; D019069:Cell Respiration / Q000187:drug effects*; D004578:Electron Spin Resonance Spectroscopy; D008081:Liposomes / Q000737:chemistry; D008567:Membranes, Artificial; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular; D009603:Nitroso Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010101:Oxygen Consumption; D010743:Phospholipids / Q000737:chemistry*; D015742:Propofol / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D013113:Spin Labels
D008081:Liposomes; D008567:Membranes, Artificial; D009603:Nitroso Compounds; D010743:Phospholipids; D013113:Spin Labels; C028992:4-nitrosophenol; D015742:Propofol