DOI: https://doi.org/10.15587/2313-8416.2015.51241

Diabetes-induced impairments in renal cortex of rats: effect of nicotinamide treatment

Леся Василівна Яніцька

Abstract


There was offered the methods of study of nicotinamide administration modeling effect (invivo) that can be realized by means of NAD and is capable to get combined with renal cortex membranes in a specific way.

The aim of research was to explore is the content of NAD and NADP and free NAD(P)/NAD(P)H pairs ratio in renal cortex changes at diabetes mellitus and nicotinamide effect.

Methods. 50 rats-males of Wistar line weighing 180–210 g. with experimental diabetes mellitus type 1 caused by single intra-abdominal administration of streptozotocin, dose – 60 mg. for 1 kg. of body weight. Animals were separated into 3 groups – the control one (C), the group of rats with diabetes mellitus type 1 (D) and rats with diabetes that underwent administration of Nam (nicotinamide) («Sigma», США), dose – 100 mg\kg of body weight during 14 days. The glucose concentration was defined using glucometer «Accu-chek» (Roshediagnostics, Swizerland).

Results. According to the data received NAD level in renal cortex was reduced to 0,179±0,012 mmol/g at diabetes against 0,259±0,023 mmol/g of tissue, Р<0,05 in the control. The NAD(P)/NAD(P)H free pairs ratio reduced to 202.0±16,1 and 0,008±0,001 in renal cortex at diabetes against 297.0±21,2 and 0.013±0.002 in the control for NAD and NADP respectively. Nicotinamide administration resulted in partial renewal of NAD level in renal cortex and NAD(P)/ NAD(P)H free pairs ratio. The modeling effect invivo of administered nicotinamide can be realized by means of NAD that is capable to get combined in renal cortex membranes in a specific way.

Conclusions. So nicotonamide takes part in regulation of kidney processes that indicates its usefulness for diabetes nephropathy treatment


Keywords


renal cortex; diabetes; nephropathy; nicotinamide; NAD; ratio; rats; experiment; model; NAD(P)/NAD(P)H pairs

References


Yang, H., Jin, X., Kei Lam, C. W., Yan, S.-K. (2011). Oxidative stress and diabetes mellitus. Clinical Chemistry and Laboratory Medicine, 49 (11), 1773–1782. doi: 10.1515/cclm.2011.250

Fiorentino, T., Prioletta, A., Zuo, P., Folli, F. (2013). Hyperglycemia-induced Oxidative Stress and its Role in Diabetes Mellitus Related Cardiovascular Diseases. Current Pharmaceutical Design, 19 (32), 5695–5703. doi: 10.2174/1381612811319320005

Popov, D. (2010). Endothelial cell dysfunction in hyperglycemia: Phenotypic change, intracellular signaling modification, ultrastructural alteration, and potential clinical outcomes. International Journal of Diabetes Mellitus, 2 (3), 189–195. doi: 10.1016/j.ijdm.2010.09.002

Dunne, J. L., Overbergh, L., Purcell, A. W., Mathieu, C. (2012). Posttranslational Modifications of Proteins in Type 1 Diabetes: The Next Step in Finding the Cure? Diabetes, 61 (8), 1907–1914. doi: 10.2337/db11-1675

Stanеv, O. І., Zaporozhchenko, O. V., Karpov, L. M. et. al (2006). Vpliv rіznih shtamіv spіrulіni na vmіst laktatu, malatu ta pіruvatu v organah shhurіv za cukrovogo dіabetu. Vіsnik Harkіvs'kogo nacіonal'nogo unіversitetu іmenі V. N. Karazіna, 4 (748), 48–53.

Kuchmerovska, T., Shymanskyy, I., Chlopicki, S., Klimenko, A. (2010). 1-Methylnicotinamide (MNA) in prevention of diabetes-associated brain disorders. Neurochemistry International, 56 (2), 221–228. doi: 10.1016/j.neuint.2009.10.004

Kuchmerovs'ka, T. M., Pentek, Ju. T., Donchenko, G. V., Janіc'ka, L. V., Guzik, M. M., Djakun, K. O. (2013). Okisljuval'nij stres u sercі shhurіv za eksperimental'nogo cukrovogo dіabetu: efekt nіkotinamіdu. Dopovіdі NAN, 8, 176–181.

Guzik, M. M., Djakun, K. O., Janіc'ka, L. V., Kuchmerovs'ka, T. M. (2013). Vpiv іngіbіtorіv polі (ADP-ribozo) polіmerazi na dejakі pokazniki oksidativnogo stresu u lejkocitah krovі shhurіv za eksperimental'nogo cukrovogo dіabetu. UBZh, 85 (1), 62–70.

Bjornstad, P., Cherney, D., Maahs, D. M. (2014). Early diabetic nephropathy in type 1 diabetes. Current Opinion in Endocrinology & Diabetes and Obesity, 21 (4), 279–286. doi: 10.1097/med.0000000000000074

Ivanac-Jancovic R., Lovcic V., Magas S., Sklebar D., Kes P. (2015). The novella about diabetic nephropathy. Acta. Clin. Croat., 54 (1), 83–91.

Bergmeyer, H. U. (Ed.) (1963). MethodsofEnzymaticAnalysis. NewYork: Academic Press Inc., 1064.

Drel, V. R., Pacher, P., Stavniichuk, R., Xu, W., Zhang, J., Kuchmerovska, T. M. et. al. (2011). Poly(ADP-ribose)polymerase inhibition counteracts renal hypertrophy and multiple manifestations of peripheral neuropathy in diabetic Akita mice. International Journal of Molecular Medicine, 28 (4), 629–635. doi: 10.3892/ijmm.2011.709

Mykuliak, T., Kuchmerovska, T. (2013). Defects of energetic processes under diabetes and its complications. Ukranian Food Journal, 2 (3), 52–56.

Belenky, P., Bogan, K. L., Brenner, C. (2007). NAD+ metabolism in health and disease. Trends in Biochemical Sciences, 32 (1), 12–19. doi: 10.1016/j.tibs.2006.11.006

Kuchmerovska, T., Shymanskyy, I., Donchenko, G., Kuchmerovskyy, M., Pakirbaieva, L., Klimenko, A. (2004). Poly (ADP-ribosyl) ation enhancement in brain cell nuclei is associated with diabetic neuropathy. Journal of Diabetes and Its Complications, 18 (4), 198–204. doi: 10.1016/s1056-8727(03)00039-4

Schreiber, V., Dantzer, F., Ame, J.-C., de Murcia, G. (2006). Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol, 7 (7), 517–528. doi: 10.1038/nrm1963

Starkov, A. A., Fiskum, G., Chinopoulos, C. et. al (2004). Mitochondrial α-Ketoglutarate Dehydrogenase Complex Generates Reactive Oxygen Species. Journal of Neuroscience, 24 (36), 7779–7788. doi: 10.1523/jneurosci.1899-04.2004

Alano, C. C., Ying, W., Swanson, R. A. (2004). Poly(ADP-ribose) Polymerase-1-mediated Cell Death in Astrocytes Requires NAD+ Depletion and Mitochondrial Permeability Transition. Journal of Biological Chemistry, 279 (18), 18895–18902. doi: 10.1074/jbc.m313329200

Xia, W., Wang, Z., Wang, Q., Han, J., Zhao, C., Hong, Y. et. al (2009). Roles of NAD/NADH and NADP+/NADPH in Cell Death. Current Pharmaceutical Design, 15 (1), 12–19. doi: 10.2174/138161209787185832

Lanaspa, M. A., Ishimoto, T., Cicerchi, C., Tamura, Y., Roncal-Jimenez, C. A., Chen, W. et. al. (2014). Endogenous Fructose Production and Fructokinase Activation Mediate Renal Injury in Diabetic Nephropathy. Journal of the American Society of Nephrology, 25 (11), 2526–2538. doi: 10.1681/asn.2013080901


GOST Style Citations


1. Yang, H. Oxidative stress and diabetes mellitus [Text] / H. Yang, X. Jin, C. W. Kei Lam, S.-K. Yan // Clinical Chemistry and Laboratory Medicine. – 2011. – Vol. 49, Issue 11. – P. 1773–1782. doi: 10.1515/cclm.2011.250

2. Fiorentino, T. V. Hyperglycemia-induced Oxidative Stress and its Role in Diabetes Mellitus Related Cardiovascular Diseases [Text] / T. V. Fiorentino, A. Prioletta, P. Zuo, F. Folli // Current Pharmaceutical Design. – 2013. – Vol. 19, Issue 32. – P. 5695–5703. doi: 10.2174/1381612811319320005

3. Popov, D. Endothelial cell dysfunction in hyperglycemia: Phenotypic change, intracellular signaling modification, ultrastructural alteration, and potential clinical outcomes [Text] / D. Popov // International Journal of Diabetes Mellitus. – 2010. – Vol. 2, Issue 3. – P. 189–195. doi: 10.1016/j.ijdm.2010.09.002

4. Dunne, L. J. Posttranslational Modifications of Proteinsin Type 1 Diabetes: The Next Stepin Findingthe Cure? [Text] / L. J. Dunne, L. Overbergh, A. W. Purcell, C. Mathieu // Diabetes. – 2012. – Vol. 61, Issue 8. – P. 1907–1914. doi: 10.2337/db11-1675

5. Станєв, О. І. Вплив різних штамів спіруліни на вміст лактату, малату та пірувату в органах щурів за цукрового діабету [Текст] / О. І. Станєв, О. В. Запорожченко, Л. М. Карпов та ін. // Вісник Харківського національного університету імені В. Н. Каразіна. – 2006. – Вип. 4, № 748. – С. 48–53.

6. Kuchmerovska, T. 1-Methylnicotinamide (MNA) in prevention of diabetes-associated brain disorders [Text] / T. Kuchmerovska, I. Shymanskyy, S. Chlopicki, A. Klimenko // Neurochemistry International. – 2010. – Vol. 56, Issue 2. – P. 221–228. doi: 10.1016/j.neuint.2009.10.004

7. Кучмеровська, Т. М. Окислювальний стрес у серці щурів за експериментального цукрового діабету: ефект нікотинаміду [Текст] / Т. М. Кучмеровська, Ю. Т. Пентек, Г. В. Донченко, Л. В. Яніцька, М. М. Гузик, К. О. Дякун // Дoповіді НАН. – 2013. – № 8. – С. 176–181.

8. Гузик, М. М. Впив інгібіторів полі (ADP-рибозо) полімерази на деякі показники оксидативного стресу у лейкоцитах крові щурів за експериментального цукрового діабету [Текст] / М. М. Гузик, К. О. Дякун, Л. В. Яніцька, Т. М. Кучмеровська // УБЖ. – 2013. – Т. 85, № 1. – С. 62–70.

9. Bjornstad, P. Early diabetic nephropathy in type 1 diabetes [Text] / P. Bjornstad, D. Cherney, D. M. Maahs // Current Opinion in Endocrinology & Diabetes and Obesity. – 2014. – Vol. 21, Issue 4. – P. 279–286. doi: 10.1097/med.0000000000000074

10. Ivanac-Jancovic, R. The novella about diabetic nephropathy [Text] / R. Ivanac-Jancovic, V. Lovcic, S. Magas, D. Sklebar, P. Kes // Acta. Clin. Croat. – 2015. – Vol. 54, Issue 1. – P. 83–91.

11. Methods of Enzymatic Analysis [Text] / H. U. Bergmeyer (Ed.). – NewYork: Academic Press Inc.б 1963. – 1064 p.

12. Drel, V. R. Poly (ADP-ribose) polymerase inhibition counteracts renal hypertrophy and multiple manifestations of peripheral neuropathy in diabetic Akita mice [Text] / V. R. Drel, P. Pacher, R. Stavniichuk, W. Xu, J. Zhang, T. M. Kuchmerovska et. al. // International Journal of Molecular Medicine. – 2011. – Vol. 28, Issue 4. – P. 629–635. doi: 10.3892/ijmm.2011.709

13. Микуляк,Т. Порушення енергетичних процесів за цукрового діабету та його ускладнень [Текст] / Т. Микуляк, Т. Кучмеровська // Ukranian Food Journal. – 2013. – T. 2, № 3. – C. 52–56.

14. Belenky, P. NAD+ metabolism in health and disease [Text] / P. Belenky, K. L. Bogan, C. Brenner // Trends in Biochemical Sciences. – 2007. – Vol. 32, Issue 1. – Р. 12–19. doi: 10.1016/j.tibs.2006.11.006

15. Kuchmerovska, T. Poly(ADP-ribosyl)ation enhancement in brain cell nuclei is associated with diabetic neuropathy athy [Text] / T. Kuchmerovska, I. Shymanskyy, G. Donchenko, M. Kuchmerovskyy, L. Pakirbaieva, A. Klimenko // Journal of Diabetes and its Complications. – 2004. – Vol. 18, Issue 4. – Р. 198–204. doi: 10.1016/s1056-8727(03)00039-4

16. Schreiber, V. Poly(ADP-ribose): novel functions for an old molecule [Text] / V. Schreiber, F. Dantzer, J.-C. Ame, G.t de Murcia // Nature Reviews Molecular Cell Biology. – 2006. – Vol. 7, Issue 7. – Р. 517–528. doi: 10.1038/nrm1963

17. Starkov, A. A. Mitochondrial α-Ketoglutarate Dehydrogenase Complex Generates Reactive Oxygen Species [Text] / A. A. Starkov, G. Fiskum, C. Chinopoulos et. al // Journal of Neuroscience. – 2004. – Vol. 24, Issue 36. – P. 7779–7788. doi: 10.1523/jneurosci.1899-04.2004

18. Alano, C. C. Poly(ADP-ribose) Polymerase-1-mediated Cell Death in Astrocytes Requires NAD+ Depletion and Mitochondrial Permeability Transition [Text] / C. C. Alano, W. Ying, R. A. Swanson // Journal of Biological Chemistry. – 2004. – Vol. 279, Issue 18. – Р. 18895–18902. doi: 10.1074/jbc.m313329200

19. Xia,W. Roles of NAD / NADH and NADP+ / NADPH in Cell Death [Text] / W. Xia, Z. Wang, Q. Wang, J. Han, C. Zhao, Y. Hong et. al // Current Pharmaceutical Design. – 2009. – Vol. 15, Issue 1. – P. 12–19. doi: 10.2174/138161209787185832

20. Lanaspa, M. A. Endogenous Fructose Production and Fructokinase Activation Mediate Renal Injury in Diabetic Nephropathy [Text] / M. A. Lanaspa, T. Ishimoto, C. Cicerchi, Y. Tamura, C. A. Roncal-Jimenez, W. Chen et. al // Journal of the American Society of Nephrology. – 2014. – Vol. 25, Issue 11. – P. 2526–2538. doi: 10.1681/asn.2013080901







Copyright (c) 2015

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

ISSN 2313-8416 (Online), ISSN 2313-6286 (Print)