Oxidative stress, progressive damage in the substantia nigra and plasma dopamine oxidation, in rats chronically exposed to ozone.

The purpose of our work was to determine the effects of oxidative stress on the neurodegeneration process in the substantia nigra, and to evaluate dopamine-oxidation metabolites in the plasma using a cyclic voltammetry (CV) technique. We have also studied the correlation between the increases in oxidized dopamine-species levels with the severity of lipid-peroxidation in the plasma. Sixty-four male Wistar rats were divided into four experimental groups and received air (Group I, control) or ozone (0.25 ppm) daily by inhalation for 4h for 15 (Group II), 30 (Group III), and 60 (Group IV) days. The brains were processed for immunohistochemical location of dopamine and p53 in the substantia nigra. Plasma collected from these animals was assayed for oxidized dopamine products using CV and lipid-peroxidation levels were measured. Our results indicate that chronic exposure to low O(3) doses causes that the number of dopaminergic neurons decreased, and p53-immunoreactive cells increases until 30 days; which was a function of the time of exposure to ozone. Oxidative stress produces a significant increase in the levels of the dopamine quinones (DAQs) that correlated well (r=0.962) with lipid peroxides in the plasma during the study period. These results suggest that DAQ could be a reliable, peripheral oxidative indicator of nigral dopaminergic damage in the brain.

Molecular structure of substituted phenylamine alpha-OMe- and alpha-OH-p-benzoquinone derivatives. Synthesis and correlation of spectroscopic, electrochemical, and theoretical parameters.

Thirteen C(6) para-substituted anilinebenzoquinones derived from perezone (PZ) (2-(1,5-dimethyl-4-hexenyl)-3-hydroxy-5-methyl-1,4-benzoquinone) were prepared to analyze the effect of the substituents on quinone electronic properties. The effect of a hydrogen bond between the alpha-hydroxy and carbonyl C(4)-O(4) groups was determined in perezone derivatives by substituting electron-donor and electron-acceptor groups such as -OMe, -Me, -Br, and -CN and comparing the -OH (APZs) and -OMe (APZms) derivatives. Reduction potentials of these compounds were measured using cyclic voltammetry in anhydrous acetonitrile. The typical behavior of quinones, with or without alpha-phenolic protons, in an aprotic medium was not observed for APZs due to the presence of coupled, self-protonation reactions. The self-protonation process gives rise to an initial wave, corresponding to the irreversible reduction reaction of quinone (HQ) to hydroquinone (HQH(2)), and to a second electron transfer, attributed to the reversible reduction of perezonate (Q(-)) formed during the self-protonation process. This reaction is favored by the acidity of the alpha-OH located at the quinone ring. To control the coupled chemical reaction, we considered both methylation of the -OH group (APZms) and addition of a strong base, tetramethylammonium phenolate (Me(4)N(+)C(6)H(5)O(-)), to completely deprotonate the APZs. Methylation led to recovery of reversible, bi-electronic behavior (Q/Q(*)(-) and Q(*)(-)/Q(2)(-)), indicating the nonacidic properties of the NH group. The addition of a strong base resulted in reduction of perezonate (Q(-)) obtained from the acid-base reaction of APZs with Me(4)N(+)C(6)H(5)O(-) to produce the dianion radical (Q(*)(2)(-)). Although the nitrogen atom interferes with direct conjugation between both rings by binding the quinone with the para-substituted ring, the UV-vis spectra of these compounds showed the existence of intramolecular electronic transfer from the respective aniline to the quinone moiety. (13)C NMR chemical shifts of the quinone atoms provided additional evidence for this electron transfer. These findings were also supported by linear variation in cathodic peak potentials (E(pc)) vs Hammett sigma(p) constants associated with the different electrochemical transformations: Q/Q(*)(-), Q(*)(-)/Q(2)(-) for APZms or HQ/HQH(2) and Q(-)/Q(*)(2)(-) for APZs. The electronic properties of model anilinebenzoquinones were determined at a B3LYP/6-31G(d,p) level of theory within the framework of the density functional theory. Our theoretical calculations predicted that all the compounds are floppy molecules with a low rotational C-N barrier, in which the degree of conjugation of the lone nitrogen pair with the quinone system depends on the magnitude of the electronic effect of the substituents of the aniline ring. Natural charges show that C(1) is more positive than C(4) although the LUMO orbital is located at C(4). Hence, if the natural charge distribution in the molecule controls the first electron addition, this should occur at carbon atom C(1). If the process is controlled by the LUMO orbitals, however, electron addition would first occur at C(4). For the APZms series susceptibility of the first reduction wave to the substitution effect (rho(pi) = 147 mV) is lower than that of the second reduction wave (rho(pi) = 156 mV). Thus, the first, one-electron transfer in the quinone system is controlled by the natural charge distribution of the molecule and therefore takes place at C(1).