Study of the cytotoxicity and antioxidant capacity of N/OFQ(1–13)NH2 and its structural analogues
Autor: | Marta Kubera, Władysław Lasoń, Monika Leśkiewicz, Rositsa Zamfirova, Margarita Kirkova, S. Todorov |
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Rok vydání: | 2009 |
Předmět: |
Male
Antioxidant Free Radicals Cell Survival Stereochemistry medicine.medical_treatment Antioxidants Lipid peroxidation Neuroblastoma chemistry.chemical_compound Cell Line Tumor medicine Animals Humans Staurosporine Rats Wistar Cytotoxicity Pharmacology Chemistry Brain Hydrogen Peroxide General Medicine Glutathione Oxidants medicine.disease Peptide Fragments Rats Nociceptin receptor Antioxidant capacity Liver Opioid Peptides medicine.drug |
Zdroj: | Pharmacological Reports. 61:1163-1172 |
ISSN: | 1734-1140 |
DOI: | 10.1016/s1734-1140(09)70179-3 |
Popis: | The effect of side-chain shortening of N/OFQ(1-13)NH(2) at position 9 ([Orn(9)]N/OFQ(1-13)NH(2), [Dab(9)]N/OFQ(1-13)NH(2), [Dap(9)]N/OFQ(1-13)NH(2)) was studied regarding potential toxicity and antioxidant capacity. Staurosporine- and H2O2-induced damage of SH-SY5Y neuroblastoma cells was not changed in the presence of N/OFQ(1-13)NH(2) and [Orn(9)]N/OFQ(1-13)NH(2), but was strongly enhanced in the presence of [Dab(9)]N/OFQ(1-13)NH(2) and [Dap(9)]N/OFQ(1-13)NH(2). Moreover, treatment of cells with the latter two analogues alone led to cell injury. Neuropeptide-dependent differences in the viability of SH-SY5Y cells were also observed, i.e., a cytoprotective effect was observed only in the presence of N/OFQ(1-13)NH(2) and [Orn(9)]N/OFQ(1-13)NH(2). Compared to [Dab(9)]N/OFQ(1-13)NH(2) and [Dap(9)]N/OFQ(1-13)NH(2), the effects of N/OFQ(1-13)NH(2) and [Orn(9)]N/OFQ(1-13)NH(2) were more beneficial in systems generating free oxygen radicals (O(2)(-) and .OH), as well as on the antioxidant status of rat brain and liver. Taken together, our findings show that N/OFQ(1-13)NH(2) and its structural analogue [Orn(9)]N/OFQ(1-13)NH(2) possess more favorable profiles than the other two nociceptin (N/OFQ) analogues. The present results suggest that shortening of the side-chain of N/OFQ(1-13)NH(2) might increase cell damage and reduce the viability of SH-SY5Y neuroblastoma cells. Moreover, such alterations may lead to changes in free-oxygen generating systems and in antioxidant status in animal tissues. |
Databáze: | OpenAIRE |
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