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
Rok vydání: 2009
Předmět:
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