Influence of nano-TiO2 on functioning of gastric smooth muscles: in vitro and in silico studies

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