Chisu, V., Lepore, M. G., Zedda, M. & Farina, V. Testosterone induces neuroprotection from oxidative stress. Effects on catalase activity and 3-Nitro-L-styrosine incorporation into -tubulin in a mouse neuroblastoma cell line. Arch. Ital. Biol. 144, 63-73

Department of Animal Biology, University of Sassari.
Archives italiennes de biologie (Impact Factor: 1.49). 06/2006; 144(2):63-73. DOI: 10.4449/aib.v144i2.882
Source: PubMed


3-nitro-L-tyrosine is formed by nitric oxide following different pathways such as NADPH oxidase, xanthine oxidase or glutamate NMDA receptor activation and is involved in the pathology of different neurological disorders. Unlike estradiol, a neuroprotective role of androgens against oxidative cell injury has not been fully investigated. This work targets the possible effects of testosterone on neuroblastoma cells exposed to 3-nitro-L-tyrosine. C1300 mouse undifferentiated neuroblastoma cells exposed to 3-nitro-L-tyrosine were cultured in the presence of testosterone. Morphological examination, proliferation and nuclear viability assays were performed. The expression of tyrosinated alpha-tubulin and incorporation of 3-nitro-L-tyrosine into protein were also estimated. Cells exposed to 3-nitro-L-tyrosine showed globular shape, reduced cytoplasmic processes and growth inhibition in comparison with controls. When testosterone was added to the medium, these changes were not evident. In addition, testosterone induced an upregulation of tyrosinated alpha-tubulin, a marker of neuronal plasticity, and a decrease in 3-nitro-L-tyrosine incorporation into tubulin. Our results suggest that testosterone exposure can diminish 3-nitro-L-tyrosine toxic effects on the morphology and growth rate of neuroblastoma cells. The upregulation of tyrosinated alpha-tubulin in testosterone-exposed cells would be consistent with concurrent plasticity events. Failure in alpha-tubulin nitration detected in cells exposed to both 3-nitro-L-tyrosine and testosterone, may support the idea that testosterone interferes with 3-nitro-L-tyrosine protein incorporation. Moreover, testosterone-induced neuroprotection likely entails a linkage with the androgen receptor as is suggested by the flutamide-induced inhibition of the hormone activity. Finally, the neuroprotective effects of testosterone in neuroblastoma cells could deal with the cellular antioxidant defence system, as shown by testosterone-induced increase in catalase activity.

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Available from: Valentina Chisu
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    • "A different effect was demonstrated for the oxidative stress – induced neuronal injury: direct antioxidant mechanism may be not involved in neuroprotection induced by androgens since micromolar concentrations of testosterone have no protective effects against cell death induced by the oxidative stressors [189]. However, other Authors previously reported conflicting results as they showed that in neuroblastoma cells, neuroprotective effects of testosterone could deal with the cellular antioxidant defense system [190] [191]. Other studies support a neuroprotective role for androgens, in which androgens can protect against oxidative stress damage [192] [193]. "
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    ABSTRACT: Anabolic-androgenic steroids (AAS) are synthetic substances derived from testosterone that are largely employed due to their trophic effect on muscle tissue of athletes at all levels. Since a great number of organs and systems are a target of AAS, their adverse effects are primarily on the following systems: reproductive, hepatic, musculoskeletal, endocrine, renal, immunological, infectious, cardiovascular, cerebrovascular, and hematological. Neuropsychiatric and behavioral effects as a result of AAS abuse are well known and described in the literature. Mounting evidence exists suggesting that in addition to psychiatric and behavioral effects, non-medical use of AAS carries neurodegenerative potential. Although, the nature of this association remains largely unexplored, recent animal studies have shown the recurrence of this AAS effect, ranging from neurotrophin unbalance to increased neuronal susceptibility to apoptotic stimuli. Experimental and animal studies strongly suggest that apoptotic mechanisms are at least in part involved in AAS-induced neurotoxicity. Furthermore, a great body of evidence is emerging suggesting that increased susceptibility to cellular oxidative stress could play a pivotal role in the pathogenesis of many neurodegenerative disorders and cognitive impairment. As in other drug-evoked encephalopathies, the key mechanisms involved in AAS – induced neuropathology could represent a target for future neuroprotective strategies. Progress in the understanding of these mechanisms will provide important insights into the complex pathophysiology of AAS-induced neurodegeneration, and will pave the way for forthcoming studies. Supplementary to abandoning the drug abuse that represents the first step in reducing the possibility of irreversible brain damage in AAS abusers, neuroprotective strategies have to be developed and implemented in future.
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    • "After administration of TES or MP, CAT levels increased significantly revealing the antioxidant activity of both drugs. Also, previous studies demonstrated the antioxidant activity of TES [10] [19] [54] [57]. Furthermore, XO is another important source of reactive oxygen species [58]. "
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    ABSTRACT: Aim: Previous studies demonstrated the neuroprotective effects of testosterone, but no previous study has examined the neuroprotective effects of testosterone on spinal cord ischemia/reperfusion injury. The purpose of this study was to evaluate whether testosterone could protect the spinal cord from ischemia/reperfusion injury. Methods: Rabbits were randomised into four groups of eight animals as follows: group 1 (control), group 2 (ischemia), group 3 (methylprednisolone) and group 4 (testosterone). In the control group only a laparotomy was performed. In all other groups, the spinal cord ischemia model was created by the occlusion of the aorta just caudal to the renal artery. Levels of malondialdehyde and catalase were analysed, as were the activities of caspase-3, myeloperoxidase, and xanthine oxidase. Histopathological and ultrastructural evaluations were performed. Neurological evaluation was performed with the Tarlov scoring system. Results: After ischemia-reperfusion injury, increases were found in caspase-3 activity, myeloperoxidase activity, malondialdehyde levels, and xanthine oxidase activity. In contrast, decreases in catalase levels were observed. After the administration of testosterone, decreases were observed in caspase-3 activity, myeloperoxidase activity, malondialdehyde levels, and xanthine oxidase activity, whereas catalase levels increased. Furthermore, testosterone treatment showed improved results concerning histopathological scores, ultrastructural score and Tarlov scores. Conclusions: Our results revealed for the first time that testosterone exhibits meaningful neuroprotective activity following ischemia-reperfusion injury of the spinal cord.
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    • "However, evidence for a causal relationship between T release and cognitive functioning is still missing. Such an association might be assumed as T has shown to have a neuroprotective role in the central nervous system (reviewed by Bialek, Zaremba, Borowicz, & Czuczwar, 2004; Chisu et al., 2006). T receptors have been found in cortex regions and the hippocampus (e.g., Beyenburg et al., 2000; Goldstein et al., 2001). "
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