Superoxide dismutase, increased levels

Zinc deficiency places an increased demand on selenium (Se) pools in daphnids. As little as 5.0 p,g Se/L in zinc-free water eliminated overt cuticle damage and substantially increased reproduction, but did not alter the shortened life span. Cladocerans at the threshold of selenium deficiency will become overtly selenium-deficient when zinc supplies are lacking. Insufficient copper introduces cuticle problems in daphnids similar to those introduced by insufficient zinc or selenium, increasing the likelihood of a proposed relation between glutathione peroxidase (which contains selenium), and copper-zinc superoxide dismutase. High levels of dietary tin increased zinc loss from rats. Zinc prevented toxic effects of vanadium (lO.Omg/kg BW) on bone metabolism of weanling rats. 

The mitochondrial dysfunctionality seen in manganese neurotoxicity might be related to the accumulation of reactive oxygen species (Verity, 1999). Mitochondrial Mn superoxide dismutase (MnSOD) is found to be low or absent in tumour cells and may act as a tumour suppressor. It is induced by inflammatory cytokines like TNF, presumably to protect host cells. In a rat model, iron-rich diets were found to decrease MnSOD activity, although a recent study reported that in rat epithelial cell cultures iron supplementation increased MnSOD protein levels and activity, but did not compromise the ability of inflammatory mediators like TNF to further increase the enzyme activity (Kuratko, 1999). 

Little information about the mechanism of action of flavonoids is anticipated from in vivo studies. The mechanism of catechin and morin seems to be related to an increase of the activity of detoxifying enzymes like glutathione-S-transferase and NADPH quinone reductase [198, 211]. Similarly, EGCG effect at the colonic level is associated to an increase in tissue superoxide dismutase levels, suggesting that it may act through a potentiation of the antioxidative defense [210]. 

Plasma malondialdehyde-like material, an indicator of lipid peroxidation, is increased in conditions of ischaemia, such as stroke [83, 84] and myocardial infarction [85]. Mitochondria extracted from hearts of vitamin-E-deficient rabbits showed a decreased mitochondrial function and an increased formation of oxygen radicals associated with a reduced superoxide dismutase activity. This was partially reversed by addition of vitamin E in vitro [86]. Measurement of in vitro susceptibility to lipid peroxidation in cardiac muscle from vitamin-E-deficient mice showed a highly significant negative correlation between the concentration of vitamin E and in vitro lipid peroxidation. The results indicate that short-term vitamin E deficiency may expose cardiac muscle to peroxidation injuries [ 87 ]. In rats, treatment for 2 days with isoprenaline increased lipid peroxide activity, as measured by malondialdehyde levels, in the myocardium. Vitamin-E-deficient animals were even more sensitive to this effect, and pretreatment with a-tocopheryl acetate for 2 weeks prevented the effect induced by isoprenaline. The authors [88] propose that free-radical-mediated increases in lipid peroxide activity may have a role in catecholamine-induced heart disease. 

It has been shown that incubation with L-dopa increased the level of GSH in neurons. The pure neuronal cultures were destroyed by incubation with L-dopa, whereas the addition of ascorbic acid or superoxide dismutase protected the cells. These results show that the upregulation of cellular GSH evoked by auto-oxidizable agents is associated with significant protection of cells. Glia play an essential role in the response of mesencephalic cell cultures. An ability to upregulate GSH may serve a protective role. 

MPTP decreases glutathione levels and increases the levels of reactive oxygen species and the degree of lipid peroxidation in mouse brain slices in vitro and increases the levels of reactive oxygen species in mouse brain in vivo. MPTP neurotoxicity in vitro is reduced by glutathione. In vitro studies have shown that MPP neurotoxicity can be reduced by vitamin E, vitamin C, coenzyme Q, and mannitol (but not by superoxide dismutase, catalase, allopurinol, or dimethyl sulfoxide). P-Carotene, vitamin C, and /V-acctylcystcine partially protect against the neurotoxic effects of MPTP in mice, as do nicotinamide, coenzyme Q, and the free-radical spin trap A-tert-butyl-a-(sulfophenyl) nitrone. 

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