Nociceptin Increases Antioxidant Expression in the Kidney, Liver and Brain of Diabetic Rats

SIMPLE SUMMARY: Nociceptin (NC) is a small peptide implicated in the physiology of pain, learning and memory. Here we investigated the role of NC in the induction of antioxidants in the kidney, liver, and the brain of diabetic rats using morphological and biochemical methods. Normal and diabetic animals were treated with NC for 5 days. Catalase (CAT) was expressed in the kidney, liver, and the neurons of the brain. Although CAT was markedly (p < 0.05) lower in the tubules of the kidney of normal and diabetic animals after NC treatment, NC significantly (p < 0.001) increased the presence of CAT in the liver and brain of diabetic rats. Superoxide dismutase (SOD) was observed in kidney tubules, hepatocytes, and neurons of the brain. Treatment with NC markedly (p < 0.001) increased the level of SOD in hepatocytes and neurons of the brain. Glutathione reductase (GRED) was seen in the convoluted tubules of the kidney, hepatocytes and neurons of the brain. Treatment with NC markedly increased (p < 0.001) the expression of GRED in kidney tubules, hepatocytes and neurons of the brain. In conclusion, NC can help diabetic patients mitigate the effects of oxidative stress by its ability to induce endogenous antioxidants. ABSTRACT: Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1–17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (p < 0.05) reduced in the kidney of normal and diabetic rats after treatment with NC. However, NC markedly (p < 0.001) increased the expression CAT in the liver and neurons of CC of diabetic rats. Superoxide dismutase (SOD) is widely distributed in the PCT and DCT of kidney, hepatocytes, and neurons of CC and hippocampus. NC significantly (p < 0.001) increased the expression of SOD in hepatocytes and neurons of CC and the hippocampus but not in the kidney. Glutathione reductase (GRED) was observed in kidney tubules, hepatocytes and neurons of the brain. NC markedly increased (p < 0.001) the expression of GRED in PCT and DCT cells of the kidney and hepatocytes of liver and neurons of CC. In conclusion, NC is a strong inducer of CAT, SOD, and GRED expression in the kidney, liver and brain of diabetic rats.