Antioxidant therapy

Bolli, R., Jeroudi, M.O., Patel, B.S., Aruoma, O.I., Halliwell, B., Lai, E.K. and McCay, P.B. (1989). Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfiision. Circ. Res. 65, 607-622. 

The effect of prolonged antioxidant therapy in relation to normal physiological processes (for example, redox cycling, cell-cell signalling, transcription factor activation) must be assessed. It is conceivable that the overload of one antioxidant by dietary supplementation (for example, a-tocopherol) may shift the levels of other antioxidants (for example, by decreasing ascorbate and /3-carotene concentrations), with unknown consequences. To assess the potential for lipid-soluble antioxidant treatment in inflammatory diseases such as RA, further investigations into these questions will be needed. 

Braganza, J.M. (1989). Towards antioxidant therapy for gastrointestinal disease. Curr. Med. Lit. Gastroenterol. 8, 99-106. 

Uden, S., Bilton, D., Nathan, L., Hunt, L.P., Main, C. and Braganza, J.M. (1990). Antioxidant therapy for recurrent pancreatitis placebo-controlled trial. Aliment. Pharmacol. Ther. 4, 357-371. 

Halliwell, B. and Gutteridge, J.M.C. (1984). Lipid peroxidation, oxygen radicals, cell damage and antioxidant therapy. Lancet ii, 1396-1397. 

Packer, L. and Viguie, C. (1989). Human exercise oxidative stress and antioxidant therapy. In Advances in Biochemistry 2 (ed. G. Benzi) pp. 1-17, John Libbey Eurotext, London. 

Other considerations such as demonstrating a direct correlation between the level of oxidative stress and tissue damage in diabetes and showing that antioxidant therapy leads to prevention, arrest or regression of diabetic complications are also important and must be the basis of future well-designed studies. 

Stress Current Status 203 7. Antioxidant Therapy Points for ... 

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

Clemens, J.A., Bhagwandin, B., Smalstig, E.G., Bennett, D.R, Mincy, R.E., Shadle, J.K. and Panetta, J.A. (1991b). Preservation of an intact functional neuronal network by antioxidant therapy in transient forebrain ischemia in rats. J. Cereb. Blood Flow Metab. 11, S145. 

Research Institute for Antioxidant Therapy, Berlin, Germany... 

Analysis of antioxidants (antioxidant status) for characterization of the anti-oxidative homeostasis in organisms by selective measurement of the ACP can be very meaningful for efficient supervision of antioxidant therapy as well. 

Chelators of transition metals, mainly iron and copper, are usually considered as antioxidants because of their ability to inhibit free radical-mediated damaging processes. Actually, the so-called chelating therapy has been in the use probably even earlier than antioxidant therapy because it is an obvious pathway to treat the development of pathologies depending on metal overload (such as calcium overload in atherosclerosis or iron overload in thalassemia) with compounds capable of removing metals from an organism. Understanding of chelators as antioxidants came later when much attention was drawn to the possibility of in vivo hydroxyl radical formation via the Fenton reaction ... 

In 1965 1967 a great interest has been attached to the possible role of free radicals in cancer after studies by Emanuel and his coworkers who reported the excessive production of free radicals in tumor cells (see, for example, Ref. [145]). On these grounds the authors suggested to apply antioxidant therapy for the treatment of cancer patients. Unfortunately, experimental proofs of overproduction of free radicals in cancer tissue turn out to be erroneous [146], A new interest in the role of free radicals in cancer development emerged after the discovery of superoxide and superoxide dismutases. 

Antioxidant therapy might be promising medication for the treatment of some lung disorders. For example, lecithinized phosphatidylcholine-CuZnSOD suppressed the development of bleomycin-induced pulmonary fibrosis in mice [284] these findings could be of relevance for the treatment of bleomycin-stimulated pulmonary fibrosis in humans. Davis et al. [285] recently demonstrated that the treatment of premature infants with recombinant human CuZnSOD may reduce early pulmonary injury. 

Figure 9.2. Mechanisms of aminoglycoside toxicity. This schematic representation summarizes the principles of aminoglycoside toxicity discussed in the text. Treatment with the drugs leads to the formation of reactive oxygen species through a redox-active complex with iron and unsaturated fatty acid or by triggering superoxide production by way of NADPH oxidase. An excess of reactive oxygen species, not balanced by intracellular antioxidant systems, will cause an oxidative imbalance potentially severe enough to initiate cell death pathways. Augmenting cellular defenses by antioxidant therapy can reverse the imbalance and restore homeostasis to protect the cell.

Moreira P. L., Smith M. A., Zhu X. W., Flonda K., Lee FI. G., Aliev G., and Perry G. (2005b). Oxidative damage and Alzheimer s disease Are antioxidant therapies useful Drug News Perspect. 18 13-19. 

Ebadi M., Srinivasan S. K., and Baxi M. D. (1996). Oxidative stress and antioxidant therapy in Parkinson s disease. Prog. Neurobiol. 48 1-19. 

Gilgun-Sherki Y., Rosenbaum Z., Melamed E., and Offen D. (2002). Antioxidant therapy in acute central nervous system injury Current state. Pharmacol. Rev. 54 271-284. 

Lenzi, A., Gandini, L., and Picardo, M. 1998. A rationale for glutathione therapy. Debate on Is antioxidant therapy a promising strategy to improve human reproduction Hum. Reprod 13,... 

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