RESUMO
Modern cutting edge technologies of chemical synthesis enable the production of unique nanostructures with excess energy and high reactivity. Uncontrolled use of such materials in the food industry and pharmacology entail a risk for the development of a nanotoxicity crisis. Using the methods of tensometry, mechanokinetic analysis, biochemical methods, and bioinformatics, the current study showed that chronic (for six months) intragastrical burdening of rats with aqueous nanocolloids (AN) ZnO and TiO2 caused violations of the pacemaker-dependent mechanisms of regulation of spontaneous and neurotransmitter-induced contractions of the gastrointestinal tract (GIT) smooth muscles (SMs), and transformed the contraction efficiency indices (AU, in Alexandria units). Under the same conditions, the fundamental principle of distribution of physiologically relevant differences in the numeric values of the mechanokinetic parameters of spontaneous SM contractions between different parts of GIT is violated, which can potentially cause its pathological changes. Using molecular docking, typical bonds in the interfaces of the interaction of these nanomaterials with myosin II, a component of the contractile apparatus of smooth muscle cells (SMC) were investigated. In this connection, the study addressed the question of possible competitive relations between ZnO and TiO2 nanoparticles and actin molecules for binding sites on the myosin II actin-interaction interface. In addition, using biochemical methods, it was shown that chronic long-term exposure to nanocolloids causes changes in the primary active ion transport systems of cell plasma membranes, the activity of marker liver enzymes and disrupts the blood plasma lipid profile, which indicates the hepatotoxic effect of these nanocolloids.
Assuntos
Actinas , Óxido de Zinco , Animais , Ratos , Simulação de Acoplamento Molecular , Trato Gastrointestinal , Proteínas do CitoesqueletoRESUMO
Using the transmission electron microscopy (TEM)/high-resolution TEM (HRTEM) and selected area electron diffraction (SAED) methods, it was shown that the nanocolloids of ZnO contain hydrolyzed ZnO nanoparticles (NPs). Typically, the nanocrystalline ZnO/Zn(OH)2 core is covered by an amorphous shell of zinc hydroxides, preventing the encapsulated crystal core from dissolving. Similar studies were carried out with TiO2 nanocolloids. It was found that burdening of rats for 30 days with a ZnO aqueous nanocolloid (AN) was accompanied by a narrowing of the amplitude range, a decrease (increase) in the frequency of spontaneous contractions (SCs), and an inhibition of the efficiency indices for smooth muscles (SMs) of the antrum and cecum. Under longer (100 days) burdening of rats with AN of ZnO, there was a tendency toward restoring the above parameters. In terms of the value and the direction of changes in most parameters for SCs of SMs, the effects (30 days) of TiO2 AN differed from those for ZnO AN and were almost the same in the case of their long-term impact. It was found that mostly M2-cholinoreceptor-dependent mechanisms of regulating the intracellular concentration of Ca2+ were sensitive to the effect of ZnO and TiO2 ANs. The molecular docking demonstrated that ZnO and TiO2 NPs did not compete with acetylcholine for the site of binding to M3 and M2 cholinoreceptors but may impact the affinity of orthosteric ligands to M2 cholinoreceptors. The studies showed that burdening rats with ZnO and TiO2 ANs was also accompanied by changes in the activity state of both intracellular enzymes and the ion transport systems for Na+, K+, and Ca2+, related to the processes of bile secretion, via the plasma membrane of hepatocytes.
RESUMO
Electronic scanning microscopy was used in the work to obtain the image and to identify the sizes of titanium dioxide (TiO2) nanoparticles 21 ± 5 nm. The qualitative and quantitative elemental analysis of the preparations of the caecum, antrum, myometrium, kidneys, and lungs of the rats, burdened with titanium dioxide, was also performed. It was established using the tenzometric method in the isometric mode that the accumulation of titanium dioxide in smooth muscles of the caecum resulted in the considerable, compared to the control, increase in the frequency of their spontaneous contractions, the decrease in the duration of the contraction-relaxation cycle, and the decrease in the indices of muscle functioning efficiency (the index of contractions in Montevideo units (MU) and the index of contractions in Alexandria units (AU)). In the same experimental conditions, there was not the increase, but the decrease in the frequency of spontaneous contractions, the duration of the contraction-relaxation cycle, and the increase in MU and AU indices in the smooth muscles of myometrium (in the group of rats, burdened with TiO2 for 30 days). It was also determined that TiO2 modulates both the mechanisms of the input of extracellular Ca2+ ions and the mechanisms of decreasing the concentration of these cations in smooth muscle cells of the caecum during the generation of the high potassium contraction. In these conditions, there is a considerable increase in the normalized maximal velocity of the contraction phase and the relaxation phase. It was demonstrated in the work that titanium dioxide also changes the cholinergic excitation in these muscles. The impact of titanium dioxide in the group of rats, burdened with TiO2, was accompanied with a considerable impairment of the kinetics of forming the tonic component of the oxytocin-induced contraction of the smooth muscles of myometrium.