IN VITRO STABILITY AND ANTIOXIDANT POTENTIAL OF THE NEUPROTECTIVE METABOLITE 6-HYDROXY-NICOTINE

Keywords: nicotine, 6-hydroxy-nicotine, Paenarthrobacter nicotinovorans, Alzheimer, oxidative stress

Abstract

Alzheimer’s disease is complex, and it is unlikely that any one single drug or intervention can successfully treat it. The implication of nicotinic acetylcholine receptors (nAChR) in Alzheimer’s disease pathogenesis has opened a new perspective on finding drugs usable for ameliorating the memory problems associated with AD. By using nAchR modulators, the availability of nAChRs for acetylcholine will be increased and the loss of forebrain cholinergic neurons associated with AD might be overcome. The microbial metabolite 6-hydroxy-D-nicotine has the ability to sustain spatial memory in rats by lowering the levels of oxidative stress in the brain and modulating the nAChRs function probably by binding to a specific site. Its success from a lab chemical to drug depends highly on its stability or shelf life. We have shown that 6-hydroxy-D-nicotine have a more potent antioxidant effect than nicotine when measured as FRAP units. Also, the pH stability of 6-hydroxy-D-nicotine is similar to nicotine, the compounds withstanding 48h exposure to pH above 3 up to 9 at room temperature.

References

1. Alzheimer’s disease Association (2018) Costs of Alzheimer’s to Medicare and Medicaid.
2. Bencherif, M., and Lippiello, P.M. (2010) Alpha7 neuronal nicotinic receptors: the missing link to understanding Alzheimer’s etiopathology? Med Hypotheses 74: 281–5
2. Bendary, E., Francis, R.R., Ali, H.M.G., Sarwat, M.I., and Hady, S. El (2013) Antioxidant and structure–activity relationships (SARs) of some phenolic and anilines compounds. Ann Agric Sci 58: 173–181
3. Benzie, I.F.F., and Strain, J.J. (1996) The Ferric Reducing Ability of Plasma (FRAP) as a Measure of “Antioxidant Power”: The FRAP Assay. Anal Biochem 239: 70–76
4. Boiangiu, R.R., Guzun, D., and Mihasan, M. (2014) Time dependent accumulation of nicotine derivatives in the culture medium of Arthrobacter nicotinovorans pAO1. Analele Stiint ale Univ “Alexandru Ioan Cuza” din Iasi Sec II a Genet si Biol Mol 15: 19–25
5. Hritcu, L., Ionita, R., Motei, D.E., Babii, C., Stefan, M., and Mihasan, M. (2017a) Nicotine versus 6-hydroxy-l- nicotine against chlorisondamine induced memory impairment and oxidative stress in the rat hippocampus. Biomed Pharmacother 86: 102–108.
6. Hritcu, L., Ionita, R., Motei, D.E., Babii, C., Stefan, M., and Mihasan, M. (2017b) Nicotine versus 6-hydroxy-l- nicotine against chlorisondamine induced memory impairment and oxidative stress in the rat hippocampus. Biomed Pharmacother 86: 102–108
7. Hritcu, L., Stefan, M., Brandsch, R., and Mihasan, M. (2013) 6-hydroxy-L-nicotine from Arthrobacter nicotinovorans sustain spatial memory formation by decreasing brain oxidative stress in rats. J Physiol Biochem 69: 25– 34
8. Hritcu, L., Stefan, M., Brandsch, R., and Mihasan, M. (2015) Enhanced behavioral response by decreasing brain oxidative stress to 6-hydroxy-l-nicotine in Alzheimer’s disease rat model. Neurosci Lett 591: 41–47
9. Mihalache, G., Babii, C., Stefan, M., Motei, D., and Marius, M. (2016) Steps towards an Arthrobacter nicotinovorans based biotechnology for production of 6-hidroxy-nicotine. In 16 th International Multidisciplinary Scientific Geoconference . pp. 341–346.
10. Mihasan, M., Capatina, L., Neagu, E., Stefan, M., and Hritcu, L. (2013) In-silico identification of 6-hydroxy-L- nicotine as a novel neuroprotective drug. Rom Biotechnol Lett 18: 8333–8340
11. Russo, P., Bufalo, A. Del, Frustaci, A., Fini, M., and Cesario, A. (2014) Beyond acetylcholinesterase inhibitors for treating Alzheimer’s disease: α7-nAChR agonists in human clinical trials. Curr Pharm Des 20: 6014–21
12. Seckar, J.A., Stavanja, M.S., Harp, P.R., Yi, Y., Garner, C.D., and Doi, J. (2008) Environmental fate and effects of nicotine released during cigarette production. Environ Toxicol Chem 27: 1505–14
13. Wang, S.N., Xu, P., Tang, H.Z., Meng, J., Liu, X.L., and Qing, C. (2005) “Green” route to 6-hydroxy-3-succinoyl- pyridine from (S)-nicotine of tobacco waste by whole cells of a Pseudomonas sp. Environ Sci Technol 39: 6877–80
14. Yu, W., Wang, R., Li, H., Liang, J., Wang, Y., Huang, H., et al. (2017) Green route to synthesis of valuable chemical 6-hydroxynicotine from nicotine in tobacco wastes using genetically engineered Agrobacterium tumefaciens S33. Biotechnol Biofuels 10: 288
Published
2018-11-07
How to Cite
Mocanu, E.-M., Mazarachi, A.-L., & Mihasan, M. (2018). IN VITRO STABILITY AND ANTIOXIDANT POTENTIAL OF THE NEUPROTECTIVE METABOLITE 6-HYDROXY-NICOTINE. Journal of Experimental and Molecular Biology, 19(3), 52-58. Retrieved from http://www.jemb.bio.uaic.ro/index.php/jemb/article/view/20
Section
Articles