Effects of structural analogues of nociceptin(1–13)NH 2 on brain antioxidant status in kainic acid‐treated rats

The in vivo effects of nociceptin (N/OFQ(1–13)NH 2 ) and its structural analogues ([Dab 9 ]N/OFQ(1–13)NH 2 , [Dap 9 ]N/OFQ(1–13)NH 2 and [Cav 9 ]N/OFQ(1–13)NH 2 ) on the levels of lipid peroxidation and cell antioxidants (enzyme and non‐enzyme) in brain of control and kainic acid (KA)‐treated rats were studied. In control animals, [Dab 9 ]N/OFQ(1–13)NH 2 and [Dap 9 ]N/OFQ(1–13)NH 2 , unlike N/OFQ(1–13)NH 2 and [Cav 9 ]N/OFQ(1–13)NH 2 , slightly increased the brain lipid peroxidation; the rest of the parameters were unchanged by all neuropeptides tested. KA (0.25 µg in 0.5 µl, i.c.v) increased the lipid peroxidation (4 and 24 h after KA‐injection) and decreased the glutathione level (1 h after KA‐administration). One hour after KA‐administration, the neuropeptides (2 µg in 0.5 µl, injected 30 min before KA) showed the following effects: a slight decrease in the KA‐induced lipid peroxidation by all nociceptin analogues and an enhancement of the KA‐decreased GSH level, but by [Cav 9 ]N/OFQ(1–13)NH 2 only. The brain antioxidant enzyme activities were unchanged in all used experimental groups. In addition, the nociceptin analogues, especially [Can 9 ]N/OFQ(1–13)NH 2 , showed a good antioxidant capacity in chemical systems, generating reactive oxygen species. In conclusion, the substitution of lysin (Lys) in N/OFQ(1–13)NH 2 molecule with other amino acids might contribute to changes in its antioxidant properties. Copyright © 2011 John Wiley & Sons, Ltd.