Effekte von Glukokortikoiden,gonadalen Steroiden und Interleukinen auf antioxidativ wirksame Substanzen und Enzymsysteme in neuronalen und glialen Zellsystemen

Zusammenfassung In Zusammenhang mit fast allen neurologischen und psychiatrischen Krankheitsbildern und dem normalen Alterungsprozess existieren heute Untersuchungen über biochemische Veränderungen von Komponenten des antioxidativen Systems. Dieses System ist für die Entgiftung von reaktiven Sauers...

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Bibliographic Details
Main Author: Schmidt, Andreas Johannes
Contributors: Heldmaier, G. (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2009
Online Access:PDF Full Text
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Summary In a large number of diseases and in the natural process of aging, alterations in the activity of antioxidant enzymes have been extensively discussed in the literature with special emphasis on the central nervous system. Additionally, altered levels of non-enzymatic compounds of the antioxidant system have been demonstrated for several diseases in the central nervous system or in peripheral body parts. The antioxidant system is responsible fore the detoxification of reactive oxygen species. The term reactive oxygen species summarizes free radicals and substances like hydrogen peroxide. Reactive oxygen species mediate the damage of macromolecules like DNA, lipids or proteins. Major enzymatic-components of the antioxidant system are the superoxide dismutase, the glutathione peroxidase and the catalase, whereas reduced glutathione or vitamin E are important non-enzymatic compounds. Various studies have described effects of steroid hormones or interleukins on the antioxidant system in peripheral organ systems like liver or kidney. In contrast, only a few studies have been published regarding the central nervous system up to now. The clinical use of steroid hormones is partially well established but still discussed controversially. The systemic administration of the synthetic glucocorticoid 6-methylprednisolone is a standard part of the therapy for spinal cord injuries. Estrogens are applied especially in the treatment of Alzheimer’s diseases. Some studies showed a benifit of estrogens and androgens on the improvement of cognitive abilities in elderly people. Summarizing the described facts, it is of great interest to examine the effects of steroids and interleukins on the antioxidant system in the central nervous system. Therefore, the aim of the present study was to examine the effects of glucocorticoids (corticosterone, dexamethasone, 6-methylprednisolone) and gonadal steroids (17β-estradiol, progesterone, testosterone) as well as interleukins (interleukin-6) on neuronal (HT22 cells, hippocampal and neocortical primary cultures of the rat) and glial (C6) cells in different concentrations and after different times of incubation. The steroids and interleukin-6 showed various effects on enzymatic and non-enzymatic compounds of the antioxidant system. One of the major effects was the increase of the content of reduced glutathione in HT22 cells after a 24 hour treatment with 6-methylprednisolone (10-7 M). In rat primary hippocampal neurons a significant increase was observed after 48 hours of incubation. This is of clinical relevance since 6-methylprednisolone is applied in the treatment of spinal traumata and its importance on the glutatione-system is discussed in the literature. In all applied cell types an incubation with 17β-estradiol (10-7 M) led to a significant increased glutathione level after a 24 hours of incubation. These results suggest that this impact of 17β-estradiol plays an important role within the scope of the various discussed neuroprotective effects of this steroid. Recent publications demonstrated also neuroprotective effects of androgens. In context with the catalase, some studies including this examination have demonstrated, that testosterone is able to increase the catalase activity. The present study showed that the increase of catalase activity induced by testosterone was associated with a neuroprotection against hydrogen peroxide. The results of the present study demonstrate that steroid hormones as well as interleukins have essentiell and neuroprotective effects on important components of the antioxidant system.