Purpose
Iodine is an essential micronutrient required for thyroid hormone biosynthesis. However, overtreatment with iodine can unfavorably affect thyroid physiology. The aim of this review is to ...present the evidence that iodine—when in excess—can interfere with thyroid hormone synthesis and, therefore, can act as a potential endocrine-disrupting chemical (EDC), and that this action, as well as other abnormalities in the thyroid, occurs—at least partially—via oxidative stress.
Methods
We reviewed published studies on iodine as a potential EDC, with particular emphasis on the phenomenon of oxidative stress.
Results
This paper summarizes current knowledge on iodine excess in the context of its properties as an EDC and its effects on oxidative processes.
Conclusion
Iodine does fulfill the criteria of an EDC because it is an exogenous chemical that interferes—when in excess—with thyroid hormone synthesis. However, this statement cannot change general rules regarding iodine supply, which means that iodine deficiency should be still eliminated worldwide and, at the same time, iodine excess should be avoided. Universal awareness that iodine is a potential EDC would make consumers more careful regarding their diet and what they supplement in tablets, and—what is of great importance—it would make caregivers choose iodine-containing medications (or other chemicals) more prudently. It should be stressed that compared to iodine deficiency, iodine in excess (acting either as a potential EDC or via other mechanisms) is much less harmful in such a sense that it affects only a small percentage of sensitive individuals, whereas the former affects whole populations; therefore, it causes endemic consequences.
Bicyclic peptides have attracted the interest of pharmaceutical companies because of their remarkable properties, putting them on a new path in medicine. Their conformational rigidity improves ...proteolytic stability and leads to rapid penetration into tissues via any possible route of administration. Moreover, elimination of renal metabolism is of great importance, for example, for people with a history of liver diseases. In addition, each ring can function independently, making bicyclic peptides extremely versatile molecules for further optimization. In this paper, we compared the potentiometric and spectroscopic properties studied by UV-vis, MCD, and EPR of four synthetic analogues of the bi-cyclic peptide c(PKKHP-c(CFWKTC)-PKKH) (BCL). In particular, we correlated the structural and spectral properties of complexes with coordinating abilities toward Cu(II) ions of MCL1 (Ac-PKKHPc(CFWKTC)PKKH-NH
) that contains the unbinding cycle and N- and C-terminal linear parts with two histidine residues, one per part; two monocyclic ligands containing one histidine residue, both in the N-terminal position, i.e., MCL2 (Ac-PKKHPc(CFWKTC)PKKS-NH
) and in the C-terminal position, i.e., MCL3 (Ac-PKKSPc(CFWKTC)PKKH-NH
), respectively; and the linear structure LNL (Ac-PKKHPSFWKTSPKKH-NH
). Potentiometric results have shown that the bicyclic structure promotes the involvement of the side chain imidazole donors in Cu(II) binding. On the other hand, the results obtained for the mono-cyclic analogues lead to the conclusion that the coordination of the histidine moiety as an anchoring group is promoted by its location in the peptide sequence further from the nonbinding cycle, strongly influencing the involvement of the amide donors in Cu(II) coordination.
Iodine deficiency is the main environmental factor leading to thyroid cancer. At the same time iodine excess may also contribute to thyroid cancer. Potassium iodate (KIO
), which is broadly used in ...salt iodization program, may increase oxidative damage to membrane lipids (lipid peroxidation, LPO) under experimental conditions, with the strongest damaging effect at KIO
concentration of ~10 mM (corresponding to physiological iodine concentration in the thyroid). Melatonin and indole-3-propionic acid (IPA) are effective antioxidative indoles, each of which protects against KIO
-induced LPO in the thyroid. The study aims to check if melatonin used together with IPA (in their highest achievable in vitro concentrations) reveals stronger protective effects against KIO
-induced LPO in porcine thyroid homogenates than each of these antioxidants used separately. Homogenates were incubated in the presence of KIO
(200; 100; 50; 25; 20; 15; 10; 7.5; 5.0; 2.5; 1.25; 0.0 mM) without/with melatonin (5 mM) or without/with IPA (10 mM) or without/with melatonin + IPA, and then, to further clarify the narrow range of KIO
concentrations, against which melatonin + IPA reveal cumulative protective effects, the following KIO
concentrations were used: 20; 18.75; 17.5; 16.25; 15; 13.75; 12.5; 11.25; 10; 8.75; 7.5; 0.0 mM. Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. Protective effects of melatonin + IPA were stronger than those revealed by each antioxidant used separately, but only when LPO was induced by KIO
in concentrations from 18.75 mM to 8.75 mM, corresponding to physiological iodine concentration in the thyroid. In conclusion, melatonin and indole-3-propionic acid exert cumulative protective effects against oxidative damage caused by KIO
, when this prooxidant is used in concentrations close to physiological iodine concentrations in the thyroid. Therefore, the simultaneous administration of these two indoles should be considered to prevent more effectively oxidative damage (and thereby thyroid cancer formation) caused by iodine compounds applied in iodine prophylaxis.
•Curcumin diminished cell viability and proliferation, and induced apoptosis in human cervical carcinoma (HeLa) cells.•Curcumin cytotoxicity was observed at low micromolar concentrations.•Curcumin ...stimulated intracellular superoxide production.•Curcumin affected nucleolar activity.•Curcumin-mediated changes in nucleolus may be a result of global DNA hypermethylation.
Curcumin, the major yellow-orange pigment of turmeric derived from the rhizome of Curcuma longa, is a highly pleiotropic molecule with the potential to modulate inflammation, oxidative stress, cell survival, cell secretion, homeostasis and proliferation. Curcumin, at relatively high concentrations, was repeatedly reported to be a potent inducer of apoptosis in cancer cells and thus considered a promising anticancer agent. In the present paper, the effects of low concentrations of curcumin on human cervical cancer (HeLa) cells were studied. We found curcumin-mediated decrease in the cell number and viability, and increase in apoptotic events and superoxide level. In contrast to previously shown curcumin cytotoxicity toward different cervical cancer lines, we observed toxic effects when even as low as 1μM concentration of curcumin was used. Curcumin was not genotoxic to HeLa cells. Because argyrophilic nucleolar protein (AgNOR protein) expression is elevated in malignant cells compared to normal cells reflecting the rapidity of cancer cell proliferation, we evaluated curcumin-associated changes in size (area) and number of silver deposits. We showed curcumin-induced decrease in AgNOR protein pools, which may be mediated by global DNA hypermethylation observed after low concentration curcumin treatment. In summary, we have shown for the first time that curcumin at low micromolar range may be effective against HeLa cells, which may have implications for curcumin-based treatment of cervical cancer in humans.
•Capsaicin exerted cytostatic rather than cytotoxic effect.•Capsaicin did not provoke apoptosis in DU145 and A549 cells when used up to 250μM.•Capsaicin stimulated intracellular reactive oxygen ...species production.•Capsaicin promoted DNA double strand breaks and chromosomal damage.•Capsaicin-induced genotoxicity may result in its limited cytotoxicity against cancer cells.
Capsaicin is the major pungent component of the hot chili peppers of the genus Capsicum, which are consumed worldwide as a food additive. More recently, the selective action of capsaicin against cancer cells has been reported. Capsaicin was found to induce apoptosis and inhibit proliferation of a wide range of cancer cells in vitro, whereas being inactive against normal cells. As data on capsaicin-induced genotoxicity are limited and the effects of capsaicin against human lung A549 and DU145 prostate cancer cells were not explored in detail, we were interested in determining whether capsaicin-associated genotoxicity may also provoke A549 and DU145 cell death. Capsaicin-induced decrease in metabolic activity and cell proliferation, and changes in the cell cycle were limited to high concentrations used (≥100μM), whereas, at lower concentrations, capsaicin stimulated both DNA double strand breaks and micronuclei production. Capsaicin was unable to provoke apoptotic cell death when used up to 250μM concentrations. Capsaicin induced oxidative stress, but was ineffective in provoking the dissipation of the mitochondrial inner transmembrane potential. A different magnitude of p53 binding protein 1 (53BP1) recruitment contributed to diverse capsaicin-induced genotoxic effects in DU145 and A549 cells. Capsaicin was also found to be a DNA hypermethylating agent in A549 cells. In summary, we have shown that genotoxic effects of capsaicin may contribute to limited susceptibility of DU145 and A549 cancer cells to apoptosis in vitro, which may question the usefulness of capsaicin-based anticancer therapy, at least in a case of lung and prostate cancer.
Fragment 85–94 of human cystatin C (FHDQPHLKRK) is interesting from a coordinating point of view. The histidine and aspartic acid residues are potential donors for copper(II) ions. We checked the ...coordination abilities of two metal ion binding domains in this peptide. The N-terminal binding site seems to be more favorable than C-terminal.
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•Fragment 85–94 from human cystatin C is interesting from a coordinating point of view.•We checked the coordination abilities for the Cu(II) ion with each of two metal ion binding sites.•NMR, potentiometric titration, UV–Vis, CD, EPR and MS studies were carried out.•In the unmodified peptide, the N-terminal binding site seems to be more favorable than C-terminal.
Human cystatin C (hCC) is one of the amyloidogenic molecules involved in neurodegeneration processes. Fragment 85–94, with the FHDQPHLKRK sequence, is interesting from the point of view of coordination as histidine and aspartic acid residues are potential copper(II) ion donors. Our previous studies showed that two potential binding sites are possible within this peptide chain. Therefore, the coordination abilities of each of these two metal ion binding sites have been checked. We have analysed two analogues of the native peptide, where particular histidine residues were substituted with alanine – an amino acid without a coordinating side chain: Ac-H2A (with alanine in position 2) and Ac-H6A (with alanine in position 6). NMR, potentiometric titration, UV–Vis, CD, EPR and MS studies were carried out. Obtained results showed that both ligands finally form the 4 N copper(II) complexes in a basic range of pH. However, their coordination properties are slightly different. The copper(II) binding efficiency is also different in both cases. Up to pH 6–6.5, AcH2A is more effective, but the situation is quite reversed under more basic conditions. Considering the results obtained, it can be concluded that in the unmodified peptide, the N-terminal binding site seems to be more favourable than the C-terminal.
► Cadmium sulfate induces aneuploidy in pig lymphocytes containing the translocated chromosome der15,17. ► The increase in aneuploidy events was exclusively seen within sub- and metacentric ...chromosomes. ► Cadmium-induced aneuploidy may be mediated by global DNA hypermethylation. ► Cadmium also promotes apoptosis, reduces cell proliferative activity and expression of nucleolar organizer regions and stimulates oxidative DNA damage.
Although cadmium is a well-established human carcinogen, the mechanisms by which it induces cancer are poorly understood. It is suggested that cadmium-mediated carcinogenesis may include the modulation of gene expression and signal-transduction pathways, interference with antioxidant enzymes, inhibition of DNA repair and DNA methylation, and induction of apoptosis. Nevertheless, no predominant mechanism playing a role in metal-induced carcinogenesis has been reported. In the present study, we used a pig Robertsonian translocation model, which is a cross between a wild boar and domestic pig resulting in Robertsonian translocation (37,XX,der15;17 or 37,XY,der15;17), to determine the role of cadmium sulfate in the modulation of genomic DNA-methylation status and the induction of aneuploidy. We found a cadmium-mediated increase in aneuploidy within chromosome group A and C, but not within chromosome group D containing the translocated chromosome der15,17 which indicates that translocated chromosome is not more prone to chromosomal aberrations than are other chromosomes. We suggest that cadmium-induced aneuploidy (up to 5-μM concentration) may be mediated by global DNA hypermethylation as monitored with HPLC and 5-mdC immunostaining. In addition, the cyto- and genotoxic potential of cadmium was evaluated. Cadmium sulfate was able to induce apoptosis, inhibit cell-proliferative status and expression of nucleolar organizer regions (NORs), and increase oxidative DNA damage (8-oxoG content).
The electrostatic impulse method is an established method for producing microbeads or capsules. Such particles have found application in biomedical engineering and biotechnology. The geometric ...properties of the droplets – constituting precursors of microbeads and capsules – can be precisely controlled by adjusting the geometry of the nozzle system, the physical properties and the flow rate of the fluids involved, as well as the parameters of the electrostatic impulse. In this work, a method of mathematical modeling of the droplet generation process using the electrostatic impulse method in a single nozzle system is presented. The developed mathematical model is an extension of the standard Volume of Fluid (VOF) model by addition of the effect of the electric field on the fluid flow. The model was implemented into the OpenFOAM toolkit for computational fluid dynamics (CFD). The performed CFD simulation results showed good agreement with experimental data. As a result, the influence of all process parameters on the droplet generation process was studied. The most significant change in droplet generation was caused by changing the electrostatic impulse strength. The presented modeling method can be used for optimization of process design and for studying the mechanisms of droplet generation. It can be extended to describe multi nozzle systems used for one-step microcapsule production.
In the present work, nanohydroxyapatites (nHAp) doped with copper and/or zinc ions were investigated for the assessment of its antibacterial activity and biocompatibility. Three forms of material ...with diverse surfaces were tested: nanopowder in colloidal suspension, galactose hydrogel (3,6-Anhydro-α-l-Galacto-β-d-Galactan) scaffold and pellet. The structural and morphological properties of the obtained biomaterials were comprehensively determined by using: XRPD, FT-IR, SEM-EDS, AAS, XPS and EPR techniques. The antimicrobial active ions, mostly Cu2+, were successfully released from the apatite structure despite the material being suspended in the porous galactose hydrogel matrix. The colloidal solutions of nanohydroxyapatites on bacterial viability revealed moderate activity of Cu2+-doped materials against Escherichia coli strain and significant activity against Pseudomonas aeruginosa strain. The comparative study of bacterial attachment to the hydrogel and pellet surface indicated that hydrogels were more prone to be colonized by both tested strains. Moreover, an additive of the Cu2+ ion modified bacterial attachment and biofilms forming on nHAp:Cu2+ and nHAp:Cu2+-Zn2+ materials. In the case of hydrogels, the biofilms were scattered while these forming on other materials were more clumped. The cytotoxicity evaluation of tested biomaterials showed biocompatible properties of both nanomaterial colloidal solutions as well as galactose hydrogel eluates toward normal mouse osteoblast cell lines (7F2) and human chondrocytes (TC28A2) and osteosarcoma cell line (U2OS). The biocompatibility of tested materials was additionally confirmed by conducting a hemolysis assay which showed full hemocompatibility of nanopowder colloidal solutions and galactose-based materials. Furthermore, unaltered red blood cell morphology was visible after a short and long time of incubation with the obtained biomaterials by using confocal laser scanning microscopy (CLSM). The comparison research provided data of 7F2, TC28 and U2OS cell attachment to the galactose hydrogel surface.
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•The influence of topography of Cu/Zn-nHAp-loaded biomaterials on the cell lines attachment and bacterial adhesion was shown.•Antibacterial activity mainly against P.aeruginosa was more visible for nanopowder (direct contact) than for hydrogel eluate.•Colloidal solutions of nanopowder and hydrogel eluate showed biocompatibility with the tested cell lines (TC28A2,U2OS, 7F2).•Greater adhesion of bacteria and eukaryotic cells was observed on hydrogels and on the rough surface of the pellets.•Perspective application of the nanohydroxyapatite co-doped with copper and zinc ions for bone implantology has been shown.
This work examines the effect of selected process parameters on the diameter of uniform and heterogeneous fibers (with and without bead-on-string structures) and the size of beads obtained during the ...electrospinning process. A 23 factorial design was performed to determine the influence of the following factors: electrical voltage, flow rate and dynamic viscosity of the poly(vinylpyrrolidone) ethanolic solution. Factorial design enables the analysis of the mathematical relationship between the chosen factors and the response with a minimum number of experiments. The factor having the most significant impact on the size of beaded fibers and beads was the solution viscosity, while the voltage had the greatest influence on the bead-free fiber diameter. The interactions between the studied factors were also analyzed. It was found that the presented method can be used for the design of an optimal and cost-effective electrospinning process, allowing the desired product to be obtained with expected features.
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