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

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.

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders

“…NOP agonism regulates the activity of neurons within these sites affecting the activity of several other neurotransmitters involved in feeding regulation. Moreover, considering the important commonalities between eating disorders and drug abuse [ 203 , 204 , 205 ] and the role of the N/OFQ-NOP system in the modulation of motivated behaviors (see paragraphs above), it is conceivable that the function of the N/OFQ-NOP system is not limited to the metabolic regulation of feeding and in the induction of endogenous antioxidants under certain conditions, such as diabetes mellitus [ 206 ]. Indeed, it plays a role in the motivation for food, possibly contributing to the etiopathology of eating disorders.…”

Drug repurposing opportunities for chronic kidney disease

“… 27 , 28 , 29 In kidney tissue, NOP has been implicated to exert direct renal effects by downregulating aquaporin-2-mediated water reabsorption and inducing endogenous antioxidants-associated nephroprotection. 30 , 31 Furthermore, preclinical and pilot clinical studies also elucidated that the NOP receptor agonist, SER100 (Serodus, ASA, Oslo, Norway), induced vasodilatation, promoted diuresis, and decreased BP, partially through their orchestration of autonomic tone and locally prejunctional inhibition of noradrenergic neurotransmission. 32 , 33 As for N/OFQ, it is ubiquitously expressed throughout the central nervous system, especially in brain regions involved in autonomic and cardiovascular control.…”

Inhibition of Endoplasmic Reticulum Stress Improves Acetylcholine-Mediated Relaxation in the Aorta of Type-2 Diabetic Rats

“…This increase in SOD activity could be a possible coping response due to the excessive production of ROS that occurs with diabetes. However, a few researchers also reported on lower SOD activity in diabetes [24,[63][64][65][66]. Chou & Tseng, in 2017, [67] demonstrated that there were no differences in SOD activity among the three groups in type-2 diabetes patients with diabetic nephropathy.…”