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
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.
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.
It is known that cognitive impairment is associated with vascular dysfunctions . 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  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  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.
This study suggests a significant effect of NAm and N-GABA in CNS linked to their neuroprotective activity for diabetic neuropathy treatment.
- 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.
- 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.
- Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012, 33(7): 829-837.