There is a body of evidence lending credence to the idea that oxidative stress may be responsible for age-related deleterious changes in brain function, and that protein carbonylation is a potential marker for such changes. An investigation of oxidative damage to mitochondrial proteins from aged rat brains was done using gel electrophoresis coupled with carbonylation-specific immunostaining. Six proteins that appeared to be susceptible to oxidative modification were identified by in-gel trypsin digestion followed by matrix-assisted laser desorption/ionization mass spectrometry and tandem mass spectrometry. Two subunits of the H(+)-transporting ATP synthase, adenine nucleotide translocator, voltage-dependent anion channel, glutamate oxaloacetate transaminase, and aconitase were identified as likely targets of age-associated carbonylation.

Ortho-quinones formed from catechol estrogens are considered prooxidants due to the production of superoxide radical anions through redox cycling via semiquinones. Para-quinols have been identified as novel metabolites of and as the major products of hydroxyl-radical scavenging by estrogens. Cycling of these compounds has also been discovered, because they are converted back to the parent estrogen via reductive aromatization in vitro and in vivo. We hypothesized that, unlike ortho-quinones, para-quinols do not induce oxidative stress due to this cycling. Like the estrogen itself, the 17β-estradiol-derived para-quinol (10β,17β-dihydroxyestra-1,4-diene-3-one) did not induce oxidative stress, as the rate of hydrogen peroxide production during the incubations of the compounds in various tissue homogenates was not significantly different from that of the control experiments performed without the addition of a test compound. We also confirmed that the estrogen metabolite estra-1,5(10)-dien-3,4,17-trione (estrone 3,4-quinone) was a profound prooxidant due to redox cycling, especially in uterine tissue. Therefore, we concluded that para-quinols do not induce oxidative stress.