Glutathione catalase

Many cellular responses protect DNA against initial genotoxic insults. Most notably, a battery of endogenous antioxidants, including glutathione, catalase, superoxide dismutase, and metallathione, can become induced in the presence of free radical formation (Cerutti et al. 1994 Boelsterli 2003). Protection by these enzymes plays... 

Two classes of antioxidants are known the low-molecular weight compounds (tocopherols, ascorbate, -carotene, glutathione, uric acid and etc.) and the proteins (albumin, transferrin, caeruloplasmin, ferritin, etc.) including antioxidant enzymes (e.g. superoxide dismutase, catalase, glutathione peroxidase). 

The red cell contains a battery of cytosolic enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, to dispose of powerful oxidants generated during its metabolism. 

Figure 4.3 Effect of a variety of anti-free-radical interventions on reperfuslon-induced ventricular fibrillation In the Isolated perfused rat heart. Regional Ischaemia was induced by occluding a snare around the left anterior descending coronary artery and, after 10 min, hearts were reperfused by releasing the snare. Superoxide dismutase (SOD) (1 x 10° U/l), catalase (CAT) (1 X 10 U/l), mannitol (Mann) (50 mM), l-methlonlne (Methlon) (10 mM), glutathione (Glutath) (10 iiM) or desferrioxamlne (Deafer) (150 iim) were included throughout the experimental time course (n = 15/group). Redrawn with permission from Bernier et af. (1986).

The free-radical defence mechanisms utilized by the brain are similar to those found in other tissues. The enzymes SOD, catalase, glutathione peroxidase, and the typical radical scavengers, ascorbate, vitamin E and vitamin A are present in the brain, as they are in peripheral tissues. However, the brain may actually be slightly deficient in some of these defence mechanisms when compared to the amounts present in other tissues. 

Marklund, S.L., Westman, N.G., Lundgren, E. and Roos, G. (1982). Copper and zincsuperoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues. Cancer Res. 42, 1955-1961. 

However, this will also prevent the formation of other cytotoxic species such as the hydroxyl radical. Further evidence that antioxidants prevent against the development of I/R injury comes from studies that show that previous ischaemic injury in the small intestine of rats results in prevention of further damage on subsequent ischaemic challenge in association with measured increases in mucosal glutathione peroxidase and catalase (Osborne et al., 1992). 

Furthermore, depletion of hepatic GSH induced chemically or by fasting augmented hepatic I/R-induced enzyme release and promoted lipid peroxidation (Jennische, 1984 Stein et al., 1991) Benoit et al. (1992) have used portacaval-shunted rats as a model of chronic hepatic ischaemia, and were able to show decreases in total levels of SOD and xanthine dehydrogenase, but no significant change in catalase or glutathione peroxidase. 

Hiraishi, H., Razandi, M., Terano, A. and Ivey, K.J. (1990). Antioxidant defenses of culture gastric mucosal cells against toxic oxygen metabolites. Role of glutathione redox cycle and endogenous catalase. Gastroenterology 98, A544. 

Higuchi, M., Cartier, L.J., Chen, M. and HoUoszy, J.O. (1985). Superoxide dismutase and catalase in skeletal muscle adaptive response to exercise. J. Gerontol. 40, 281-286. Hunter, M.I.S., Brzeski, M.S. and de Vane, P.J. (1981). Superoxide dismutase, glutathione peroxidase and thiobarbi-turic acid-reactive compounds in erythrocytes in Duchenne muscular dystrophy. Clin. Chim. Acta 115, 93-98. 

Kar, N.C. and Pearson, C.M. (1979). Catalase superoxide dismutase, glutathione reductase and thiobarbituric acid-reactive products in normal and dystrophic human muscle. Clin. Chim. Acta 94, 277-280. 

Normally, the cascade from oxygen to water is well controlled by SOD, catalase and endogenous antioxidants such as glutathione, ascorbate and vitamin E. Vitamin E is the most important membrane-bound antioxidant. However, during ischaemia, the local control of ROS is lost, thus reactive free radicals can attack the membranes and lipid peroxidation begins. Endogenous antioxidants can be supplemented. This section describes this supplementation strategy. 

Garlic s proven mechanisms of action include (a) inhibition of platelet function, (b) increased levels of two antioxidant enzymes, catalase and glutathione peroxidase, and (c) inhibition of thiol enzymes such as coenzyme A and HMG coenzyme A reductase. Garlic s anti-hyperlipidemic effects are believed to be in part due to the HMG coenzyme A reductase inhibition since prescription medications for hyperlipidemia have that mechanism of action (statins). It is unknown whether garlic would have the same drug interactions, side effects, and need for precautions as the statins. 

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