GVS-111 prevents oxidative damage and apoptosis in normal and Down's syndrome human cortical neurons
| Autor: | Carlos Hoyo-Vadillo, Alejandra Pelsman, Tatiana A Gudasheva, Rita U. Ostrovskaya, Jorge Busciglio, S. B. Seredenin |
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| Rok vydání: | 2003 |
| Předmět: |
Apoptosis
Pharmacology medicine.disease_cause Neuroprotection Antioxidants Nootropic Lipid peroxidation chemistry.chemical_compound Developmental Neuroscience Pregnancy Reference Values medicine Humans Ferrous Compounds Cells Cultured Noopept Cerebral Cortex Neurons Neurodegeneration Piracetam Dipeptides Hydrogen Peroxide medicine.disease Oxidative Stress Neuroprotective Agents Biochemistry chemistry Mechanism of action Aborted Fetus Female medicine.symptom Down Syndrome Oxidative stress Developmental Biology medicine.drug |
| Zdroj: | International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 21(3) |
| ISSN: | 0736-5748 |
| Popis: | The neuroprotective activity of a novel N-acylprolyl-containing dipeptide analog of the nootropic 2-oxo-1-pyrrolidine acetamide (Piracetam) designated as GVS-111 (DVD-111/Noopept) was tested in two in vitro models of neuronal degeneration mediated by oxidative stress: normal human cortical neurons treated with H(2)O(2), and Down's syndrome (DS) cortical neurons. Incubation of normal cortical neurons with 50 microM H(2)O(2) for 1h resulted in morphological and structural changes consistent with neuronal apoptosis and in the degeneration of more than 60% of the neurons present in the culture. GVS-111 significantly increased neuronal survival after H(2)O(2)-treatment displaying a dose-dependent neuroprotective activity from 10nM to 100 microM, and an IC(50) value of 1.21+/-0.07 microM. GVS-111 inhibited the accumulation of intracellular free radicals and lipid peroxidation damage in neurons treated with H(2)O(2) or FeSO(4), suggesting an antioxidant mechanism of action. GVS-111 exhibited significantly higher neuroprotection compared to the standard cognition enhancer Piracetam, or to the antioxidants Vitamin E, propyl gallate and N-tert-butyl-2-sulpho-phenylnitrone (s-PBN). In DS cortical cultures, chronic treatment with GVS-111 significantly reduced the appearance of degenerative changes and enhanced neuronal survival. The results suggest that the neuroprotective effect of GVS-111 against oxidative damage and its potential nootropic activity may present a valuable therapeutic combination for the treatment of mental retardation and chronic neurodegenerative disorders. |
| Databáze: | OpenAIRE |
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