Redox-Potential and Immune- Endothelial Axis States of Pancreases in Type 2 Diabetes Mellitus in Experiments

Abstract Background: Disturbances in mitochondrial complex1 functioning plays a crucial role in the pathogenesis of β-cells dysfunction in pancreas in diabetic mellitus (DM), and the redox-potential is a contributing factor to redox imbalance, pseudo hypoxia and chronic inflammation. The objective of this study was to assess the correlation between changes in redox-potential and inflammation response of blood and pancreases in streptozotocin (STZ)-nicotinamide (NA) induced DM in rats and ability of various pharmacological agents to its correction. Materials and methods: In randomized controlled study in rats with DM type 2 (T2DM) induced by i.p. injection of 110 mg/kg NA 15 min before intravenously injection of 65 mg/kg of STZ the redox-immune axis disturbances and efficacy of various pharmacological agents to its correction was study. The selected cohort of T2DM animals were randomized into 5 groups dependent of 21 days receiving therapy: control II - 1 ml of 0.9% NaCl, main I - metformin 350 mg/ kg, main II –glibenclamide 0.6 mg/kg, main III- Nadcin®, 16 mg/kg, main IV- metformin, 100 mg/kg +Nadcin® 16 mg/kg, and V mainglibenclamide 0,3 mg/kg and Nadcin®, 16 mg/kg. Results: Treatment with glibenclamide, metformin, Nadcin® or its combination significantly decreased the glucose and increased insulin levels. Nadcin® alone or in combination brought towards normal levels of HbA1c and endothelin-1 (ET-1), fully restored the pool of oxidized NAD(P) and the level of redox-potentials. Changes in the level of ET-1 correlated with deterioration of redox-potential NAD/NADH and NADP/NADPH in pancreatic cells. Treatment with Nadcin® decreased the level of TNF-α, nuclear factor kappa B (NFkB) and increased the level of IL-10. The same effect observed in combined treatment of Nadcin® with antiheprglicemic drugs in ½ doses of its action in monotherapy. Treatment with metformin decease the level of IL-6, but not TNF-α and NF-kB activity. Conclusion: Redox potential imbalance represents a therapeutic target for T2DM and trigger for disturbances in innate immunity system activity. Course treatment with NAD-containing drug, Nadcin restores functioning of pancreases cells and inhibits proinflammatory cytokines releases that does not occurs under treatment with oral hypoglycemic agents.