Central nervous system free-radical damage

Sadrzadeh, S.M.H. and Eaton, J.W. (1992). Hemt obin-induced oxidant damage to the central nervous system. In Free Radical Mechanisms of Tissue Injury (eds. M.T. Moslen and C.V. Smith) pp. 24—32. CRC Press, Boca Baton. 

Floyd, R.A. (1997). Protective action of nitrone-based free radical traps against oxidative damage to the central nervous system. Adv. Pharmacol. 38 361-78. 

Orr (43) used dimethyl sulfoxide as a free radical sink to inhibit the effect of Cu and ascorbic acid on catalase and 8-glucuronidase as well as the degradation of hyaluronic acid. The formation of a radical from ascorbic acid and Cu in water was detected by EPR (44). Based on an EPR spectroscopic study of ascorbic acid during oxidation of methyl-arachidonate-enriched liposomes, ascorbic acid may be important in preventing free radical damage in the central nervous system (45). 

Redox chemistry and ageing recent findings on the role of Mn(II) in free radical dismutation or disproportionation, with related consequences for cell damage vs. protection, seem to indicate potential connections with various disease states of the nervous and circulatory systems. These include Alzheimer s disease, arteriosclerosis, plus the connection between diabetes and damage to the motor and central nervous systems. 

The pathophysiological significance of the acute burst in HO and lipid peroxidation in the hippocampus is underscored by the pre-ischaemic or pre-hypoxic treatment with free radical scavengers or antioxidants in attenuating the selective CAl damage associated with these models. The current state of antioxidant therapy in acute central nervous system injury was recently reviewed by Gilgun-Sherki et al. (2002). 

Methyl - 4 - phenyl -1,2,3,6 - tetrahydropyridine (MPTP) is a frequently used animal model for Parkinson s disease. When injected into animals, MPTP is taken up by the cells in the substantia nigra where monoamino oxidase B (EC 1.4.3.4) converts it to l-methyl-4-phenylpyridinium ion (MPP ). This ion induces free radicals and duplicates many of the signs of Parkinson s disease in animals. In mice melatonin attenuated the resulting damage in the central nervous system (Acuna-Castroviejo et al. 1997). MPTP-induced neural lipid peroxidation was reduced to control levels when melatonin was co-administered with the herbicide. Neuronal loss and MPTP-induced reduction of tyrosine hydroxylase (EC 1.14.16.2) activity in neurones of the striatum were attenuated by melatonin. 

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