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ECPB 2017, 78(2): 31–36
https://doi.org/10.25040/ecpb2017.02.031
Research articles

Renoprotective Effect of Nicotinamide under experimental Diabetes

L. YANITSKA1, T. TYKHONENKO2, I. PRYVROTSKA3, T. KUСHMEROVSKA2
Abstract

One of the most severe complications of diabetes mellitus is diabetic nephropathy. It was previously revealed that nicotinamide (NAm) exerts strong neuroprotective effect and can be efficient in brain abnormalities induced by type 1 diabetes. More evidences have been emerged indicating that besides being essential for energy transduction, the intermediates of the NAD metabolism have a variety of significant regulatory roles, some of which are involved in fundamental cellular processes. The study has been designed to establish the potential benefit under development of diabetic nephropathy from nicotinamide, the NAD biosynthesis precursor, on the ratio of free the NAD / NADH and the NADP / NADPH couples, which regulates numerous fundamental cellular processes. All studies were performed after 6 weeks of the streptozotocin-induced diabetes (60 mg/kg of body weight, i.p.) in rats treated for 14 days with or without nicotinamide (100 mg/kg, i.p.). Content of the NAD and the intermediates of the NAD metabolism were assayed enzymatically. Research into the renal tissues energetic revealed that compared with the NAD content in control, this in the renal tissues of diabetic rats was decreased by 31 %, p < 0.05. This may be due to the inhibition of energy processes, as well as the dysfunction of the NAD(P)-dependent dehydrogenases and other the NAD-dependent processes, in particular mono- and poly-ADP-ribosylation. At the condition of decreased the NAD content in kidney tissue of diabetic animals, the ratio of free the NAD / NADH and the NADP / NADPH couples also were decreased by 32 % and 38 %, respectively. The established changes in the studied parameters indicate that the development of diabetic nephropathy under hyperglycemia is due to a violation of both energy and regulatory processes in the kidney tissues. Administration of nicotinamide was accompanied by a partial restoration of energy processes and normalizition of the ratio of free the NAD(P) / NAD(P)H couples, as it is evidenced by an increase in the NAD content in renal tissue and improvment of regulatory processes for preventing of diabetic nephropathy in rats. Moreover, the albumin level in the daily urine of diabetic rats treated by NAm decreased by 29 %, that resulted in inhibition of the development of microangiopathy in rat kidney tissue thereby preventing cell death in the kidneys. The obtained results show that the alterations of the NAD content and the ratio of free the NAD(P) / NAD(P)H couples play an important role under diabetic nephropathy which accompanied by the development of micro- and macrovascular complications in kidneys. The findings suggest that renoprotective effects of nicotinamide should proceed towards the simultaneous protections of kidney cells against impairments of energetic processes and enhanced endogenous oxidant burden. Beneficial effects of NAm treatment offer a non-toxic, well tolerated and rational option for the complex therapy of diabetic nephropathy, that will improve the quality and life expectancy of patients with this complication of diabetes mellitus.

Keywords: diabetes mellitus, nephropathy, nicotinamide, NAD, ratio of free NAD(P) / NAD(P)H couples

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