Biol. Stud. 2019: 13(1); 3–26 • DOI: https://doi.org/10.30970/sbi.1301.592

INFLUENCE OF NANO-TiO2 ON FUNCTIONING OF GASTRIC SMOOTH MUSCLES: IN VITRO AND IN SILICO STUDIES

O. V. Tsymbalyuk, A. M. Naumenko, T. L. Davydovska

Abstract


Nanosized materials, including titanium dioxide nanoparticles, sized under 10 nm, are systems with an excessive energy and high chemical activity, while the nanoparticles of about (1–3) nm enter the reactions with other chemical compounds practically without any activation energy which predetermines the formation of substances with new properties. The energy accumulated by these objects first of all is determined by the uncompensated nature of the bonds between surface and near-surface atoms that is a reason of superficial phenomena. Taking the abovementioned into consideration, it was interesting to study the influence of nano-titanium dioxide sized (1–3) nm and (4–8) nm on the functioning of rat gastric smooth muscles in vitro and in silico.

The tenzometric method in the isometric mode was used to demonstrate that titanium dioxide suspensions with nanoparticles, sized (4–8) and (1–3) nm, change the structure of spontaneous contraction cycles for circular stomach smooth muscles of antrum in rats with a decrease in their total efficiency (a decrease in index of contractions in Montevideo units (MU) and the index of contractions in Alexandria units (AU)). In these conditions, there was also a change in the kinetic parameters of high potassium contractions and the contractions induced by acetylcholine, the mediator of acetylcholine receptors. There was also an impairment of the processes of coordinating the velocities of contractions and relaxations, that are more expressed in the first case at the effect of titanium dioxide (1–3) nm, and in a second one – (4–8) nm. The molecular docking of titanium dioxide nanoparticle to an extracellular part of a muscarinic acetylcholine M2 type receptor demonstrated a possibility of forming the bonds with some amino acids of the site of its allosteric modulator, that impacts the affinity of this receptor to the orthosteric ligands. The binding site of titanium dioxide does not compete for binding sites of this type of acetylcholine receptor neurotransmitter by its amino acid composition. The molecular docking of titanium dioxide to the muscarinic acetylcholine M3 type receptor showed that there are common amino acid residues for both the nanoparticle and acetylcholine with which bonds are formed in the orthosteric binding site. This suggests that at this binding site there can be a competitive relationship between titanium dioxide and acetylcholine within the site.

Keywords: tenzometric method, circular smooth muscles, titanium dioxide, molecular docking, muscarinic acetylcholine receptors

 


Full Text:

PDF

References


1. Baryliak A.Yu., Besaha Kh.S., Bobytsky Ya.V., Vakhula Ya.I. Nanocatalysts based on titanium (IV) oxide: synthesis and properties (Overview). Physics and chemistry of a solid body. 2009; 10(3): 515-523.

2. Bock A., Merten N., Schrage R., Dallanoce C., Bätz J., Klöckner J., Schmitz J., Matera C., Simon K., Kebig A., Peters L., Müller A., Schrobang-Ley J., Tränkle C., Hoffmann C., De Amici M., Holzgrabe U., Kostenis E., Mohr K. The allosteric vestibule of a seven transmembrane helical receptor controls G-protein coupling. Nat Commun., 2012; 3: 1044.
https://doi.org/10.1038/ncomms2028
PMid:22948826 PMCid:PMC3658004

3. Bolton T.B., Zholos A.V. Activation of M2 muscarinic receptors in guinea-pig ileum opens cationic channels modulated by M3 muscarinic receptors. Life Sci., 1997; 60(13-14): 1121-1128.
https://doi.org/10.1016/S0024-3205(97)00056-8

4. Burdyga Th.V., Kosterin S.A. Kinetic analysis of smooth muscle relaxation. Gen. Physiol. Biophys. 1991; 10:589-598.

5. Chekman I.S., Hovorukha M.O., Doroshenko A.M. Nanogenotoxicology: impact of nanoparticles on a cell. Ukrainian medical periodical, 2011; 1: 30-35.

6. Cho W.S., Kang B.C., Lee J.K., Jeong J., Che J.H., Seok S.H. Comparative absorption, distribution, and excretion of titanium dioxide and zinc oxide nanoparticles after repeated oral administration. Particle and fibre toxicology, 2013; 10: 9-14.
https://doi.org/10.1186/1743-8977-10-9
PMid:23531334 PMCid:PMC3616827

7. Duhovny D., Nussinov R., Wolfson H.J. Efficient unbound docking of rigid molecules. Proceedings of the Fourth International Workshop on Algorithms in Bioinformatics, 2002; 2452: 185-200.
https://doi.org/10.1007/3-540-45784-4_14

8. Eglen R.M. Muscarinic receptors and gastrointestinal tract smooth muscle function. Life Sci., 2001; 68(22-23): 2573-2578.
https://doi.org/10.1016/S0024-3205(01)01054-2

9. Fahmi A., Minot C., Silvi B., Cause M. Theoretical analysis of the structure of titanium dioxide crystals. Physical Review B., 1993; 47(18): 11717-11724.
https://doi.org/10.1103/PhysRevB.47.11717

10. Filippov I.B. Involvement of secondary intracellular mediators in the mechanisms of purinergic inhibition of interstitial smooth muscles. Neurophysiology. 2010; 42(3): 192-198.
https://doi.org/10.1007/s11062-010-9145-5

11. Furness J.B. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol., 2012; 9: 286-294.
https://doi.org/10.1038/nrgastro.2012.32
PMid:22392290

12. Goroshchenko Y.G. Chemistry of Titanium. Kyiv: Scientific thought. 1970: 416 p. (In Russian)

13. Gregory K.J., Sexton P.M., Christopoulos A. Allosteric modulation of muscarinic acetylcholine receptors. Curr Neuropharmacol., 2007; 5(3): 157-167.
https://doi.org/10.2174/157015907781695946
PMid:19305798 PMCid:PMC2656816

14. Kato T., Nakamura E., Imaeda K., Suzuki H. Modulation of the activity of two pacemakers by transmural nerve stimulation in circular smooth muscle preparations isolated from the rat proximal colon. J. Smooth Muscle Res., 2009; 45(6): 249-268.
https://doi.org/10.1540/jsmr.45.249
PMid:20093794

15. Kim K.D., Kim S.H., Kim H.T. Applying the taguchi method to the optimization for the synthesis of TiO2 nanoparticles by hydrolysis of TEOT in micelles. Colloids Surf. A., 2005; 254(1-3): 99-105.
https://doi.org/10.1016/j.colsurfa.2004.11.033

16. Kim S., Thiessen P.A., Bolton E.E., Chen J., Fu G., Gindulyte A., Han L., He J., He S., Shoemaker B.A., Wang J., Yu B., Zhang J., Bryant S.H. PubChem Substance and Compound databases. Nucleic Acids Res., 2016; 44: 1202-13.
https://doi.org/10.1093/nar/gkv951
PMid:26400175 PMCid:PMC4702940

17. Kobaiasi N. Introduction to nanotechnology. Publishing House: Binom. Laboratory of Knowledge. 2008, 134 p.

18. Kovtun G.P, Verevkin A.A. Nanomaterials: nanotechnologies and material science: Overview. Kharkov: NNC KhFTI, 2010, 73 p.

19. Kruse A.C., Ring A.M., Manglik A., Hu J., Hu K., Eitel K., Hьbner H., Pardon E., Valant C., Sexton P.M., Christopoulos A., Felder C.C., Gmeiner P., Steyaert J., Weis W.I., Garcia K.C., Wess J., Kobilka B.K. Activation and allosteric modulation of a muscarinic acetylcholine receptor. Nature, 2013; 504(7478): 101-106.
https://doi.org/10.1038/nature12735
PMid:24256733 PMCid:PMC4020789

20. Kuemmerle J.F., Murthy K.S., Makhlouf G.M. Agonist-activated, ruanodine-sensitive, IP3-insensitive Ca2+ release channels in longitudinal muscle of intestine. Am. J. Physiol., 1994; 266: 1421-1431.
https://doi.org/10.1152/ajpcell.1994.266.5.C1421
PMid:7515567

21. Li X.L., Peng Q., Yi J.X., Wang X.,Y. Li Y.D. Near monodisperse TiO2 nanoparticles and nanorods. Chem. Eur. Journal, 2006; 12(8): 2383-2391.
https://doi.org/10.1002/chem.200500893
PMid:16374889

22. Lu Z.L., Lindner E., Mayer H.A. Applications of sol-gel-processed interphase catalysіs. Chem. Rev., 2002; 102(10): 3543-3578.
https://doi.org/10.1021/cr010358t
PMid:12371893

23. Maltsev P.P. Nanotechnologies. Nanomaterials. Nanosystem equipment. Moscow: Technosphere. 2008, 438 p.

24. O'Neil K.T., DeGrado W.F. A thermodynamic scale for the heliх-forming tendencies of the commonly occurring amino acids. Science, 1990; 250(4981): 646-651.
https://doi.org/10.1126/science.2237415
PMid:2237415

25. Parala A., Devi R., Bhakta R., Fischer R.А., Parala H. Synthesis of nano-scale TiO2 particles by a nonhydrolytic approach. J. Mater. Chem., 2002; 12: 1625-1627.
https://doi.org/10.1039/b202767d

26. Paul H.R, Berg K.M., Urban N.H., Miner A.S. Regulation of smooth muscle calcium sensitivity: KCl as a calcium-sensitizing stimulus. Am J Physiol Cell Physiol, 2005; 288: 769-783.
https://doi.org/10.1152/ajpcell.00529.2004
PMid:15761211

27. Qazi Mohd. S.J. Elucidation of mechanism of carcinogenesis by environmental carcinogens and their prevention by nanoparticles: an in silico study. Lucknow, India: Integral University. 2014: 190 р.

28. Schneidman-Duhovny D., Inbar Y., Nussinov R., Wolfson H.J. PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Research, 2005; 33(Web Server issue): W363-367.
https://doi.org/10.1093/nar/gki481
PMid:15980490 PMCid:PMC1160241

29. Scientific opinion. Re-evaluation of titanium dioxide (E 171) as a food additive. EFSA Journal, 2016; 14(9): е04545.
https://doi.org/10.2903/j.efsa.2016.4545

30. Shuba M.F., Vladimirova I.A., Philippov I.B. Mechanisms of the inhibitory action of neurotransmitters of smooth muscle. Neurophysiol., 2003; 35(3-4): 224-233.
https://doi.org/10.1023/B:NEPH.0000008783.45729.d5

31. Tang J., Redl Y., Zhu T., Siegrist T., Brus L.E., Steigerwald M.L. An organometallic synthesis of TiO2 nanoparticles. J Nano Lett., 2005; 5(3): 543-548.
https://doi.org/10.1021/nl047992h
PMid:15755111

32. Tsymbalyuk O.V., Shirkin L.A. Ecological safety of nanoparticles, nanomaterials and nanotechnologies, textbook. Vladimir State University. - Vladimir: Publishing house of the Vladimir State University, 2009, 64 p.

33. Тsymbalyuk O.V., Naumenko A.M., Nyporko A.Yu., Davidovska T.L., Skryshevsky V.A. Excitation-inhibition of stomach smooth muscles by the nano-sized titanium dioxide materials. Dopov. Nac. akad. nauk Ukr., 2015; 10: 85-92.
https://doi.org/10.15407/dopovidi2015.10.085

34. Tsymbalyuk O.V., Naumenko A.M., Rohovtsov O.O., Skoryk M.A., Voiteshenko I.S., Skryshevsky V.A., Davydovska T.L. Titanium dioxide modulation of the contractibility of visceral smooth muscles in vivo. Nanoscale Research Letters, 2017; 12(1): 1-12.
https://doi.org/10.1186/s11671-017-1865-7
PMid:28235365 PMCid:PMC5318306

35. Tsymbalyuk O.V., Naumenko A.M., Skoryk M.A., Nyporko A.Yu., Davidovska T.L., Skryshevsky V.A. Histamine- and nicotine-stimulated modulations of mechanic activity of smooth muscles in gastrointestinal tract at the impact of nanosized ТіО2 material. Biopolym. Cell, 2016; 32(2): 140-149.
https://doi.org/10.7124/bc.000917

36. Wang Y., Suzek T., Zhang J., Wang J., He S., Cheng T., Shoemaker B.A., Gindulyte A., Bryant S.H. PubChem BioAssay: 2014 update. Nucleic Acids Res., 2014; 42(1): 1075-82.
https://doi.org/10.1093/nar/gkt978
PMid:24198245 PMCid:PMC3965008

37. Ward S.M., Sanders K.M. Involvement of intramuscular interstitial cells of Cajal in neuroeffector transmission in the gastrointestinal tract. J. Physiol., 2006; 576: 675-682.
https://doi.org/10.1113/jphysiol.2006.117390
PMid:16973700 PMCid:PMC1890401

38. Ward S.M., Ordog T., Koh S.D., Baker S.A., Jun J.Y., Amberg G., Monaghan K., Sanders K.M. Pacemaking in intestinal cells of Cajal depends upon calcium handling by endoplasmic reticulum and mitochondria. J. Physiol., 2000; 527: 149-162.

39. Zhang C., Vasmatzis G., Cornette J.L., DeLisi C. Determination of atomic desolvation energies from the structures of crystallized proteins. Journal of Molecular Biology, 1997; 267: 707-726.
https://doi.org/10.1006/jmbi.1996.0859
PMid:9126848

40. Zhao J., Castranova V. Toxicology of nanomaterials used in nanomedicine. Toxicol Environ Health B Crit Rev., 2011; 14(8): 593-632.
https://doi.org/10.1080/10937404.2011.615113
PMid:22008094




DOI: http://dx.doi.org/10.30970/sbi.1301.592

Refbacks

  • There are currently no refbacks.


Copyright (c) 2019 Studia biologica