Study of the cytotoxicity and antioxidant capacity of N/OFQ(1–13)NH2 and its structural analogues

The effect of side-chain shortening of N/OFQ(1–13)NH2 at position 9 ([Orn9]N/OFQ(1–13)NH2, [Dab9]N/OFQ(1–13)NH2, [Dap9]N/OFQ(1–13)NH2) 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)NH2 and [Orn9]N/OFQ(1–13)NH2, but was strongly enhanced in the presence of [Dab9]N/OFQ(1–13)NH2 and [Dap9]N/OFQ(1–13)NH2. 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)NH2 and [Orn9]N/OFQ(1–13)NH2. Compared to [Dab9]N/OFQ(1–13)NH2 and [Dap9]N/OFQ(1–13)NH2, the effects of N/OFQ(1–13)NH2 and [Orn9]N/OFQ(1–13)NH2 were more beneficial in systems generating free oxygen radicals (O2− and OH), as well as on the antioxidant status of rat brain and liver. Taken together, our findings show that N/OFQ(1–13)NH2 and its structural analogue [Orn9]N/OFQ(1–13)NH2 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)NH2 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.