Kainic acid (KA) is a known potent neuroexcitotoxin, although the biochemical mechanism producing its underlying neurotoxic effect is not quite clear. Histopathological examination of gerbil brains 24 h after systemic injection of KA revealed severe neuronal lesions in different regions of the brain, especially the cerebellar and hippocampal areas. We have detected free radical formation in the brain 1 h after KA administration by using an in vivo spin trapping technique. We have also observed increased lipid peroxidation in the brain after KA-treatment by analyzing thiobarbituric acid reactive substances and conjugated diene formation. Diminished brain specific (Na+, K+)-ATPase activity was also found 2 h after KA injection and persisted to 24 h. It is possible that the free radical reaction is a primary cause of neuronal degeneration after KA administration.
Electron spin resonance (ESR) spectroscopy was used to gain insight at the molecular level into the curing of bone cement. Methyl methacrylate was polymerized using a N,N-dimethyl-p-toluidine (TD)/benzoyl peroxide (BPO) redox system in the presence of polymethyl methacrylate (PMMA) powder. The conventional nine-line ESR spectrum for the growing polymer radical was detected at the gel stage of polymerization. While the optimum free radical concentration was observed near the equimolar amine/BPO concentration, excess amine led to a change in the chemical structure of the trapped radical and inhibited the polymerization process. At a high amine/BPO ratio the nine-line signal disappeared and a three-line nitroxide-based radical appeared. The appearance of this nitroxide signal seems to depend on the amine/BPO molar ratio and on the presence of PMMA. An excess amount of amine with respect to BPO was found to inhibit the polymerization process. When BPO was removed, the system still polymerized but with a longer gelation time and a lower radical concentration. These results demonstrate that trapped free radicals in the bulk polymerization of MMA convert to polymeric peroxides that act as initiators in bone cement. When the accelerator 4-dimethylamino phenethyl alcohol (TDOH) was used, a higher radical concentration was observed in the polymerizing system. TDOH shows potential for being a more effective accelerator than TD for bone cement curing.
ESR spin trapping technique was used to detect and analyze free radical formation. When 6-hydroxydopamine (6-OHDA) was incubated alone or in the presence of a free radical generating system (H2O2 and FeSO4), hydroxyl free radicals were observed in a concentration-dependent manner. Glutathione was found to be the most effective scavenger of the ESR signal when compared with vitamin E or Mannitol. The addition of ethanol resulted in the formation of the pure hydroxyethyl free radicals. The amount of hydroxyethyl free radicals in the system was dependent upon the concentration of ethanol and the formation of hydroxyethyl free radicals correlated well with the extent of lipid peroxidation and the loss of enzymic activity of the membrane-bound (Na+,K+)-ATPase. We suggest that in the biological system ethanol may potentiate the neurotoxicity of 6-OHDA with the formation of hydroxyethyl free radicals, which are longer-lived and far more damaging to membranes than the hydroxyl radicals. These data lead us to further hypothesize that the neuronal degeneration caused by 6-OHDA and other compounds that generate free radicals could be potentiated in the presence of ethanol.
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