Nicotinamide and Nicotinoyl-Gaba in Prevention of Experimental Diabetic Neuropathy

image_print

Nicotinamide and Nicotinoyl-Gaba in Prevention of Experimental Diabetic Neuropathy

Kuchmerovska T.M. 1*, Tykhonenko T.M.1, Guzyk M.M.1 , Tykhomyrov A.O.1, Yanitska L.V.2
1Department of Biochemistry of Vitamins and Coenzymes, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, 9 Leontovicha St., 01030 Kyiv, Ukraine
2Bogomolets National Medical University, 13, T. Shevchenko blvd., 01601 Kyiv, Ukraine

Corresponding author:  Prof. Kuchmerovska T.M., PhD, Tel:38 (044)2347178, Fax:38(044)2796365; Email: tkuchmerovska@gmail.com or kuch@biochem.kiev.ua

Introduction

Diabetic neuropathy is associated with development of cognitive dysfunction and structural and metabolical alterations in brain.  We aimed to evaluate the potential benefit of nicotinamide (NAm) and nicotinoyl-GABA (N-GABA), conjugate of nicotinic acid and GABA, administration on alterations in the expressions of nuclear factor kappa B (NF-kB), neuronal nitric oxide synthase (nNOS) and vascular endothelial growth factor (VEGF) in brain of diabetic rats.

Material and Methods

All studies were performed after 6 weeks of type 1 diabetes (streptozotocin, 60 mg/kg of b. w.) in male Wistar rats treated for two weeks with or without NAm (100 mg/kg, i. p.) or N-GABA (55 mg/kg, i. p.). The expression of  NF-kB, nNOS and VEGF was assessed by immunoblotting.

Results

It is known that cognitive impairment is associated with vascular dysfunctions [1]. Indeed, we have shown that in brain of diabetic rats the expression of VEGF was decreased by 52 % as compared to control and it was normalized by NAm but effect of N-GABA was more profound than in control. In diabetic rat brains expression of total NF-κB, a transcription factor [2] was  increased by 2,7 time vs control, p<0.05. NAm caused a slight lowering effect on expression NF-κB while N-GABA was more pronounced. We assess nNOS [3] expression and revealed it l was decreased by 1,4 time as compared to control. Both NAm or N-GABA treatment lead to an increase of NOS in brain by 1,8 and 1,3 times respectively vs diabetes, p<0.05. We found out the  neuronal cytoskeleton alterations in diabetic brain, confirmation of that are decreased expression of neurofilaments light chain (NF-L) by 1,8 time, medium chain (NF-M) by 2,1 time as compared to control, while heavy chain (NF-H) wasn’t changed. Slight increasing effects of both NAm or N-GABA were observed on expression of NF-M, their effect on expression of NF-L was more profound for N-GABA.

Conclusion

This study suggests a significant effect of NAm and N-GABA in CNS linked to their neuroprotective activity for diabetic neuropathy treatment.

References

    1. Taylor SL, Trudeau D, Arnold B, Wang J, Gerrow K et al. VEGF can protect against blood brain barrier dysfunction, dendritic spine loss and spatial memory impairment in an experimental model of diabetes. Neurobiol Dis. 2015, 78: 1-11.
    2. Mollah ZU, Pai S, Moore C, O’Sullivan BJ, Harrison MJ. Abnormal NF-kappa B function characterizes human type 1 diabetes dendritic cells and monocytes. J Immunol. 2008, 180(5): 3166-3175.
    3. Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012, 33(7): 829-837.

Be the first to comment on "Nicotinamide and Nicotinoyl-Gaba in Prevention of Experimental Diabetic Neuropathy"

Leave a comment

Your email address will not be published.


*