Free radicals Glucocorticoids

Glucocorticoids are recommended for the treatment of CNS disorders as they stabilize microvas-cular permeability, reduce edema formation, reduce intracranial pressure, decrease oxygen-derived free radicals and prevent post-traumatic autodestruction of nervous tissue. Their clinical use in equine medicine includes the treatment of brain and spinal cord trauma, cerebral edema associated with neonatal maladjustment syndrome (NMS), endotoxic shock and EPM. This is despite the fact that the safety and efficacy of glucocorticoids in the treatment of many types of nervous system inflammation has not been established and their use and dosing schedules continue to be debated. 

In certain cases, steroid hormones were converted into corresponding radical intermediates in either enzymatic or non-enzymatic systems (Ko-DADMA et al. 1997). Although detection of the free radicals was limited to oestrogens, evidence suggests that glucocorticoids as well as androgens may also share the physiological formation of free radicals. 

Sanchez ER, Toft DO, Schlesinger MJ, Pratt WB (1985) Evidence that the 90-kDa phosphoprotein associated with the untransformed L-cell glucocorticoid receptor is a murine heat shock protein. J Biol Chem 260 12398-12401 Sato M, Bremner I (1993) Oxygen free radicals and metallothionein. Free Radic Biol Med 14 325-337... 

Although both metals and glucocorticoids can directly induce MT synthesis, divalent metals like cadmium and zinc are the best-known inducers of MT synthesis. Metal-responsive elements (MREs) and glucocorticoid-responsive elements (GREs) have been identified in MT genes (Palmiter 1987). In addition to these inducers, several other compounds (which do not even bind with MT), oxidative stress, and inflammatory conditions have been shown to induce MT synthesis in various systems. Several mechanisms are proposed for such induction of MT synthesis and they may involve lipid peroxidation with free radical formation, release of cytokines during inflammation, and changes in tissue distribution of zinc. 

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