Evaluation of the antioxidant properties of propofol and its nitrosoderivative. comparison with homologue substituted phenols.
Propofol (2,6-diisopropylphenol), some substituted phenols (2,6-dimethylphenol and 2,6-ditertbutylphenol) and their 4-nitrosoderivatives have been compared for their scavenging ability towards 1,1-diphenyl-2-picrylhydrazyl and for their inhibitory action on lipid peroxidation. These products were also compared to the classical antioxidants butylated hydroxytoluene and butylated hydroxyanisole. When measuring the reactivity of the various phenolic derivatives with 1,1-diphenyl-2-picrylhydrazyl the following order of effectiveness was observed: butylated hydroxyanisole > propofol > 2,6-dimethylphenol > 2,6-di-tertbutylphenol > butylated hydroxytoluene. In cumene hydroperoxide-dependent microsomal lipid peroxidation, propofol acts as the most effective antioxidant, while butylated hydroxyanisole, 2,6-di-tertbutylphenol and butylated hydroxytoluene exhibit a rather similar effect, although lower than propofol. In the iron/ascorbate-dependent lipid peroxidation propofol, at concentrations higher than 10 microM, exhibits antioxidant properties comparable to those of butylated hydroxytoluene and butylated hydroxyanisole, 2,6-Dimethylphenol is scarcely effective in both lipoperoxidative systems. The antioxidant properties of the various molecules depend on their hydrophobic characteristics and on the steric and electronic effects of their substituents. However, the introduction of the nitroso group in the 4-position almost completely removes the antioxidant properties of the examined compounds. The nitrosation of the aromatic ring of antioxidant molecules and the consequent loss of antioxidant capacity can be considered a condition potentially occurring in vivo since nitric oxide and its derivatives are continuously formed in biological systems.
Rigobello
Maria Pia
MP
Department of Biological Chemistry, University of Padova, Viale G. Colombo 3, 35121 Padova, Italy.
Stevanato
Roberto
R
Momo
Federico
F
Fabris
Sabrina
S
Scutari
Guido
G
Boscolo
Rita
R
Folda
Alessandra
A
Bindoli
Alberto
A
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010851:Picrates / Q000737:chemistry; D015742:Propofol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
D000975:Antioxidants; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D005609:Free Radicals; D010636:Phenols; D010851:Picrates; C004931:1,1-diphenyl-2-picrylhydrazyl; D015742:Propofol