Reactive Oxygen Species Production Is Responsible for Antineoplastic Activity of Osmium, Ruthenium, Iridium and Rhodium Half-Sandwich Type Complexes with Bidentate Glycosyl Heterocyclic Ligands in Various Cancer Cell Models

Platinum complexes are used in chemotherapy, primarily as antineoplastic agents. In this study, we assessed the cytotoxic and cytostatic properties of a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich-type complexes with bidentate monosaccharide ligands. We identified 5 compounds with moderate to negligible acute cytotoxicity but with potent long-term cytostatic activity. These structure-activity relationship studies revealed that: 1) osmium(II) p-cymene complexes were active in all models, while rhodium(III) and iridium(III) Cp* complexes proved largely inactive; 2) the biological effect was influenced by the nature of the central azole ring of the ligands—1,2,3-triazole was the most effective, followed by 1,3,4-oxadiazole, while the isomeric 1,2,4-oxadiazole abolished the cytostatic activity; 3) we found a correlation between the hydrophobic character of the complexes and their cytostatic activity: compounds with O-benzoyl protective groups on the carbohydrate moiety were active, compared to O-deprotected ones. The best compound, an osmium(II) complex, had an IC50 value of 0.70 µM. Furthermore, the steepness of the inhibitory curve of the active complexes suggested cooperative binding; cooperative molecules were better inhibitors than non-cooperative ones. The cytostatic activity of the active complexes was abolished by a lipid-soluble antioxidant, vitamin E, suggesting that oxidative stress plays a major role in the biological activity of the complexes. The complexes were active on ovarian cancer, pancreatic adenocarcinoma, osteosarcoma and Hodgkin’s lymphoma cells, but were inactive on primary, non-transformed human fibroblasts, indicating their applicability as potential anticancer agents.

What Is the Cause of Toxicity of Silicone Oil?

Purpose: To investigate the toxicity of the low-molecular-weight components (LMWCs) in ophthalmic silicone oils (SilOils) on retinal cell lines. Methods: The toxicity of six types of LMWCs were studied and compared with conventional SilOil 1000 cSt. In vitro cytotoxic tests of LMWCs, in both liquid and emulsified forms, on three retinal cell lines (Müller cells (rMC-1), photoreceptor cells (661W) and retinal pigment epithelial cells (ARPE-19)) were conducted using a transwell cell culturing system. The morphology and viability of cells were assessed by light microscopy and Cell Counting Kit-8 (CCK-8) assay at different time points (6, 24 and 72 h). The ARPE-19 apoptotic pathway was investigated by Mitochondrial Membrane Potential/Annexin V Apoptosis Kit at different time points (6, 24 and 72 h). Results: Apart from dodecamethylpentasiloxane (L5), all liquid LMWCs showed varying degrees of acute cytotoxicity on retinal cell lines within 72 h. Emulsified LMWCs showed comparable cytotoxicity with liquid LMWCs on retinal cell lines. Cyclic LMWCs, octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) had significantly higher cytotoxicity when compared with their linear counterparts decamethyltetrasiloxane (L4) and L5 with similar molecular formula. Using ARPE-19 cells as an example, we showed that LMWCs induce the apoptosis of retinal cells. Conclusions: Most LMWCs, in both liquid and emulsified forms, can induce acute cytotoxicity. In addition, cyclic LMWCs are suspected to have higher cytotoxicity than their linear counterparts. Therefore, LMWCs are suspected to be the main cause of the long-term toxicity of ophthalmic SilOil, due to their toxicity and propensity to cause ophthalmic SilOil to emulsify. The amount of LMWCs should be considered as the paramount parameter when referring to the quality of SilOil.

Differential proliferative and cytotoxic effect of selected components of essential oils on human glioblastoma cells

Background: In the study of bioactive agents from traditional medicine, mono- and sesquiterpenes represent the main ingredients of essential oils. Till now, only thymoquinone and perillyl alcohol have been clinically tested on glioblastoma. Objective: In the present study, we examined the effect of ten different essential oils on three human glioblastoma cell lines and one healthy human cell line. Methods: We used confocal laser scanning microscopy, flow cytometry, and cell growth analysis to evaluate cell morphology changes, membrane disruption effects, acute cytotoxicity and effects on the proliferation rate caused by the essential oils pinene, geraniol, eucalyptol, perillaldehyde, limonene, and linalool, perillyl alcohol, myrcene, bisabolol and valencene on human cells. Caspase 3/7 activity was measured to observe apoptosis induced by the essential oils. Results: We found that the cytotoxicity concentrations varied not only between different essential oils but also among different cell lines. Acute cytotoxicity of essential oils was based on cell membrane disruption and that HEK cells were affected to a much higher degree than the Glioblastoma cells. Vacuoles found in surviving glioblastoma cells appeared to be a factor in this effect. Conclusion: Caspase activity did not correlate with the membrane damage observed in the flow cytometry experiments. This is especially evident in the HEK cells that only showed apoptosis with two out of ten essential oils.

Crosslinking Efficacy and Cytotoxicity of Genipin and Its Activated Form Prepared by Warming It in a Phosphate Buffer: A Comparative Study

The aim of the present study was to compare the acute and cumulative cytotoxicity of intact (n-GE) and warmed genipin (w-GE), while investigating the differences in crosslinking capabilities of these two genipins by rheological and mechanical tests. The n-GE solution was prepared by dissolving genipin powder in a sodium phosphate buffer solution. The w-GE solution was prepared by warming the n-GE solution at 37 °C for 24 h. The mechanical tests for chitosan (CH)/genipin gels showed the crosslinking rate of w-GE was much greater than that of n-GE up until 6 h after preparation, whereas the degree of crosslinking of CH/n-GE gels became higher at 12 h. The ISO 10993-5 standard method, which is established specifically for evaluating cumulative cytotoxicity, determined equivalent IC50 for w-GE (0.173 mM) and n-GE (0.166 mM). On the other hand, custom-made cytotoxicity tests using a WST-8 assay after 1 h of cultivation showed that the acute cytotoxicity of w-GE was significantly higher than that of n-GE at concentrations between 0.1–5 mM. The acute cytotoxicity of w-GE should be taken into consideration in its practical uses, despite the fact that the much faster crosslinking of w-GE is useful as an effective cross linker for in-situ forming gels.

Evidence that nano-TiO2 induces acute cytotoxicity to the agronomically beneficial nitrogen fixing bacteria Sinorhizobium meliloti

When nano-sized titanium dioxide (nano-TiO2) absorbs ultra-violet (UV-A) radiation, it produces reactive oxygen species that can be toxic to bacteria. We used the agronomically beneficial nitrogen-fixing bacterium Sinorhizobium meliloti strain 1021 as a model microorganism to detect nano-TiO2 toxicity. S. meliloti was exposed to aqueous dispersions of micrometer-sized TiO2 (micron-TiO2, 44 μm) or nanometer-sized TiO2 (nano-TiO2, 21 nm) at nominal concentrations of 0, 100, 300, 600, 900 and 1800 mg TiO2/L. There were fewer viable S. meliloti after exposure to nano-TiO2 under dark and UV-A light conditions. Nano-TiO2 was more toxic to S. meliloti with UV-A irradiation (100% mortality at 100 mg TiO2/L) than under dark conditions (100% mortality at 900 mg TiO2/L). Micron-TiO2 concentrations less than 300 mg TiO2/L had no effect on the S. meliloti viability under dark or UV-A light conditions. Exposure to 600 mg/L or more of micron-TiO2 under UV-A light could also photo-kill S. meliloti cells (100% mortality). Further study is needed to ascertain whether nano-TiO2 interferes with the growth of N2-fixing microorganisms in realistic agricultural environments.

The effectiveness of a nonalcoholic disinfectant containing metal ions, with broad antimicrobial activity

Disinfectants have different efficacies depending on their use and the target microorganism. This study aimed to evaluate the efficacy and safety of our new nonalcoholic disinfectant, which consists mainly of metal ions. According to the 17th revised Japanese Pharmacopoeia and ASTM international E1052 method, the bactericidal and virucidal efficacy of this new disinfectant against 13 microorganisms was evaluated by the in vitro quantitative suspension test. Additionally, the disinfectant cytotoxicity against multiple cell lines was examined. Then, a safety test using a human open patch test was performed with 26 healthy volunteers. This disinfectant showed strong bactericidal and virucidal activities: all microorganisms except enterovirus were inactivated very quickly. The infectivity of 12 microbial strains was eliminated within 5 min of disinfectant exposure. Additionally, this disinfectant showed little acute cytotoxicity in vitro. All volunteers were negative in the human open patch test. Our new disinfectant has a broad spectrum of microbial targets, is safe for human skin, and demonstrates no cytotoxicity. This disinfectant could prevent common microbial infections.

Tribological changes of tooth enamel-mullite/3Y-TZP couple in artificial saliva

In-situ mullite toughened 3Y-TZP composite ceramic (mullite/3Y-TZP) with excellent mechanical properties was fabricated by gel-casting. The cytotoxicity of mullite/3Y-TZP was determined by both extract and direct contact methods, and the results indicated that mullite/3Y-TZP had no acute cytotoxicity. Furthermore, the tribological properties of the tooth enamel sliding against mullite/3Y-TZP in artificial saliva were investigated by using the pin-on-plate friction method. The friction coefficient (μ) between the two friction samples was about 0.464 with a stable friction process, and both of them showed slight wear. Analysis of the wear surface and debris demonstrated that the tooth enamel mainly suffered from fatigue wear accompanied by mild adhesive wear, while mullite/3Y-TZP showed slight abrasive wear. This result indicated that mullite/3Y-TZP had good wear resistance and showed potential applications in dental material.

Tribological changes of tooth enamel-mullite/3Y-TZP couple in artificial saliva

In-situ mullite toughened 3Y-TZP composite ceramic (mullite/3Y-TZP) with excellent mechanical properties was fabricated by gel-casting. The cytotoxicity of mullite/3Y-TZP was determined by both extract and direct contact methods, and the results indicated that mullite/3Y-TZP had no acute cytotoxicity. Furthermore, the tribological properties of the tooth enamel sliding against mullite/3Y-TZP in artificial saliva were investigated by using the pin-on-disk friction method. The friction coefficient (µ) between the two friction samples was about 0.464 with a stable friction process, and both of them showed slight wear. Analysis of the wear surface and debris demonstrated that the tooth enamel mainly suffered from fatigue wear accompanied by mild adhesive wear, while mullite/3Y-TZP showed slight abrasive wear. This result indicated that mullite/3Y-TZP had good wear resistance and showed potential applications in dental material.