Rampant online marketing of teeth whitening products: Evaluation of online information, labelling accuracy and quantitative analysis of high peroxide content gels.

Background: /Purpose: Online vendors seize the advantage of the high demand on home-use, do-it-yourself dental bleaching products. The study aims to present the uncontrolled online market of dental products and provide evidence of consumer safety risks associated with the utilization of high peroxide content bleaching products without dentist's supervision, and also to identify misleading and insufficient information on content and compromised product quality. Materials and methods: A complex risk-based methodology was used including website content evaluation focusing on ingredients, precautionary statements and directions for use provided by online retailers. Bleaching products were test procured in which packaging and labels were documented and assessed. Quality control was performed using the permanganometric method per the official European Pharmacopoeia. Results: One (16.7%) of six test procured peroxide gels was not delivered. Another arrived without enclosed description or instructions. The ingredient list was incomplete or missing for all (100%) online products, however, it was listed on the label or in enclosed documentation in four out of five (80%) samples. Precautionary statements were scarcely (16.7%) disclosed online, contrarily, safety claims were emphasized by most (83.3%) websites. Contraindications and adverse effects were mentioned in the majority (80%) of the delivered product labels. One sample contained no active principle, in two sample' peroxide content exceeded the label's claim by 5.2-9.0% while in another two it was below the concentration indicated on the labels by 79.9-80.7%. Conclusions: Dissimilarity in regulations elicits an opportunity for consumers to purchase inappropriately labeled, questionable quality, high peroxide content dental products without information regarding ingredients, application and risks. The uncontrolled market, easy access and unsupervised application of high peroxide-content teeth whiteners imply patient safety issues.

Novel cyclic C5-curcuminoids penetrating the blood-brain barrier: Design, synthesis and antiproliferative activity against astrocytoma and neuroblastoma cells.

Novel series of cyclic C5-curcuminoids 17a-j and 19-22 were prepared as cytotoxic agents and evaluated against human neuroblastoma (SH-SY5Y) or human grade IV astrocytoma (CCF-STTG1) cell lines in low (∼0.1 nM - 10 nM) concentrations. Among the tested 21 derivatives, 16 displayed potent antiproliferative activity with IC50 values in the low nanomolar to picomolar range (IC50 = 7.483-0.139 nM). Highly active compounds like N-monocarboxylic derivative 19b with IC50 = 0.139 nM value against neuroblastoma and N-alkyl substituted 11 with IC50 = 0.257 nM against astrocytoma proved some degree of selectivity toward non-cancerous astrocytes and kidney cells. This potent anticancer activity did not show a strong correlation with experimental logPTLC values, but the most potent antiproliferative molecules 11-13 and 19-22 are belonging to discrete subgroups of the cyclic C5-curcuminoids. Compounds 12, 17c and 19b were subjected to blood-brain barrier (BBB) penetration studies, too. The BBB was revealed to be permeable for all of them but, as the apparent permeability coefficient (Papp) values mirrored, in different ratios. Lower toxicity of 12, 17c and 19b was observed toward primary rat brain endothelial cells of the BBB model, which means they remained undamaged under 10 µM concentrations. Penetration depends, at least in part, on albumin binding of 12, 17c and 19b and the presence of monocarboxylic acid transporters in the case of 19b. Permeation through the BBB and albumin binding, we described here, is the first example of cyclic C5-curcuminoids as to our knowledge.

Different effects of two cyclic chalcone analogues on redox status of Jurkat T cells.

Chalcones are intermediary compounds of the biosynthetic pathway of the naturally flavonoids. Previous studies have demonstrated that chalcones and their conformationally rigid cyclic analogues have tumour cell cytotoxic and chemopreventive effects. It has been shown that equitoxic doses of the two cyclic chalcone analogues (E)-2-(4'-methoxybenzylidene)-(2) and (E)-2-(4'-methylbenzylidene)-1-benzosuberone (3) have different effect on cell cycle progress of the investigated Jurkat cells. It was also found that the compounds affect the cellular thiol status of the treated cells and show intrinsic (non-enzyme-catalyzed) reactivity towards GSH under cell-free conditions. In order to gain new insights into the cytotoxic mechanism of the compounds, effects on the redox status and glutathione level of Jurkat cells were investigated. Detection of intracellular ROS level in Jurkat cells exposed to 2 and 3 was performed using the dichlorofluorescein-assay. Compound 2 did not influence ROS activity either on 1 or 4h exposure; in contrast, chalcone 3 showed to reduce ROS level at both timepoints. The two compounds had different effects on cellular glutathione status as well. Compound 2 significantly increased the oxidized glutathione (GSSG) level showing an interference with the cellular antioxidant defence. On the contrary, chalcone 3 enhanced the reduced glutathione level, indicating enhanced cellular antioxidant activity. To investigate the chalcone-GSH conjugation reactions under cellular conditions, a combination of a RP-HPLC method with electrospray ionization mass spectrometry (ESI-MS) was performed. Chalcone-GSH adducts could not be observed either in the cell supernatant or the cell sediment after deproteinization. The investigations provide further details of dual - cytotoxic and chemopreventive - effects of the cyclic chalcone analogues.

Kinetic analysis of some chalcones and synthetic chalcone analogues on the fenton-reaction initiated deoxyribose degradation assay.

Investigation of in vitro hydroxyl radical scavenging (antioxidant) effect 4-methoxychalcone (1a) and its cyclic analogues (2a-4a), as well as their hydroxyl substituted counterparts (1b-4b) was performed by means of the Fenton-reaction initiated deoxyribose degradation assay in short term (10 minute) and long term (240 minute) experiments. The kinetic deoxyribose method provides possibility to investigate not only the short term antioxidant (hydroxyl radical scavenger) effect but the possible late prooxidant effect of the tested substances as well. In the short term studies compounds 2a, 2b and 4b showed the most pronounced antioxidant effect. The long-term studies showed that the antioxidant activity of all the tested compounds but 4a can be well characterized by the short time determination of the thiobarbituric acid (TBA)-reactive substances (TBARS). Experiments in the presence of ethylenediaminetetraacetic acid (EDTA) resulted in a substantially reduced degradation of deoxyribose in each incubation. Similar to the respective experiment performed without EDTA, the TBARS level of the incubations with 4a showed an increase over the 60-120 minute period. The results demonstrated that complex forming activities that can modify microspeciation and reactivity of iron ions can lead to different short term antioxidant efficiency of the tested substances. Results of the long term incubations indicated that chemical transformation of the tested substances can result formation of derivatives that can initiate further redox activities under the experimental conditions.

Design, synthesis and antiproliferative activity of some 3-benzylidene-2,3-dihydro-1-benzopyran-4-ones which display selective toxicity for malignant cells.

A series of 3-benzylidene-4-chromanones 1a-l were prepared and their cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 lymphoid leukemia cells were compared to the previously generated biodata in these three assays for the isosteric 2-benzylidene-1-tetralones 2a-l. Over 40% of the compounds in series 1 were more potent than their counterparts in series 2, while equipotency was noted in one-third of the comparisons made. In general the IC(50) values of 1a-l towards the human T-lymphocytes were in the low micromolar range. Molecular modelling revealed differences in shapes of representative molecules in series 1 and 2 which may contribute to the variation in cytotoxic potencies. Most of the compounds in series 1 displayed greater potencies towards HSC-2, HSC-3, HSC-4 and HL-60 neoplasms than HGF, HPC, and HPLF normal cells and were well tolerated in mice.

Different effects of two cyclic chalcone analogues on cell cycle of Jurkat T cells.

It has been previously shown that the cyclic chalcone analogues E-2-(4'-methoxybenzylidene)- (2) and E-2-(4'-methylbenzylidene)-1-benzusuberone (3) inhibited proliferation of various murine and human tumor cells. In order to gain new insights into the cytotoxic mechanism of the two compounds detection of apoptosis and necrosis of Jurkat T cells exposed to 2 and 3 were performed by flow cytometry using the Annexin V-FITC and propidium iodide double staining method. Analysis of the DNA histograms at 8, 24 and 48 h exposure times showed that near equitoxic doses of 2 and 3 had different effects on the cell cycle of the exposed cells. The immediate (8h) effect of 2 was a remarkable decrease of cells in the G(0)/G(1) phase and increase in the G(2)/M phase. This effect could also be seen in the histogram of cells at the 24h time point. On the contrary, such an effect of 3 could not be observed. At the 24 and 48 h time points accumulation of sub-G(0) (apoptotic and necrotic) and hyperdiploid cells could be detected after both treatments. Incubation of 2 and 3 with reduced glutathione under cell-free conditions indicated spontaneous conjugation (non-redox) reaction at pH 7.4 and pH 9.0. Analyzing the mechanism of action the total thiol content of the cells exposed to compounds 2 and 3 was determined. Compound 2 showed to reduce the total cellular thiol level both under nutrient-free and nutrient-supplemented conditions. Under the latter conditions an increase of the total thiol level of the cells exposed to 3 for 4h could be observed. The different effect of the two compounds on the cellular thiol status might contribute to the different tumor cytotoxicity of the cyclic chalcone analogues 2 and 3. Investigation of antioxidant capacity of the compounds by monitoring time course of the Fenton-reaction initiated in vitro degradation of 2-deoxyribose indicated that both compounds displayed hydroxyl radical scavenger activity. The experiments provide further details of dual--cytotoxic and cytoprotective (chemopreventive)--effects of the compounds.

Effect of the chalcone analog E,E-bis(2-hydroxybenzylidene) acetone on the 7,12-dimethylbenz[a]anthracene-induced Ha-ras gene activity in vivo.

The chalcone analog E,E-bis(2-hydroxybenzylidene)acetone (HBA) was found to display strong NAD(P)H:quinone reductase (NQO1) inducer potency in Hepa 1c1c7 cells. In order to determine whether this promising chemopreventive activity would extend to anticarcinogenic properties, the effect of HBA on the 7,12-dimethylbenz[a]anthracene (DMBA)-induced expression of the Ha-ras gene in isolated RNA from liver, lung, kidney, spleen, thymus, lymph nodes and bone marrow of CBA/Ca inbred mice was investigated. DMBA is a well-known chemical carcinogen, which can act as initiator by causing point mutations in certain oncogenes and tumor suppressor genes. According to the previous results, elevated Ha-ras expression has been noted even 24 h after DMBA treatment. Administration of HBA simultaneously with DMBA resulted in a decrease of the DMBA-induced Ha-ras gene expression in all the investigated tissues. This observation suggests metabolic interaction of HBA and DMBA. Administration of HBA 24 h prior to the DMBA treatment reduced the Ha-ras gene expression in all the tissues but the liver, where a slight elevation could be detected. This latter effect could be the result of a possible CYPIA inducer and pro-oxidant effects of HBA. The pro-oxidant effect of HBA can be taken into consideration based on its previously demonstrated GSH-reactivity and the present results obtained by investigation of the time-course of Fenton reaction-initiated degradation of 2-deoxyribose in the presence of HBA.

[Effect of some nonsteroid antiinflammatory drugs on Fenton-reaction initiated degradation of 2-deoxy-D-ribose]. / Néhány nem-szteroid gyulladáiscsökkento hatásának vizsgálata a 2-dezoxi-D-ribóz Fenton-reakció inicializálta degradáiciójára.

The authors examined the possible interactions of some nonsteroidal anti-inflammatory drugs with hydroxyl radicals by means of the test based on degradation of 2-deoxy-D-ribose initiated by hydroxyl radicals. The method is based on spectrophotometric measurement of thiobarbituric acid (TBA)-reactive carbonyl compounds that are formed in the degradation reaction of 2-deoxy-D-ribose by hydroxyl radicals (HO*) generated in the Fenton-reaction between iron(II)-ions and hydrogen peroxide (H2O2). The authors studied the degradation-inhibitory effect of phenacetin, paracetamol (acetaminophen), indomethacin, ibuprofen, diclofenac sodium, salicylic acid and salicylamide used in 100 microM and 200 microM concentrations, in the present or without addition of EDTA. In the short term (10 minute) studies paracetamol and salicylic acid proved to show the most effective degradation inhibitory effect. In the longer-time (120 minute) studies after the early inhibitory effect of paracetamol, indometacine and salicylic acid, an increase of the TBA-reactive compounds could be observed.