Phytantriol.

The Expert Panel for Cosmetic Ingredient Safety reviewed updated information that has become available since their original assessment from 2007, along with updated information regarding product types, and frequency and concentrations of use, and reaffirmed their original conclusion that Phytantriol is safe as a cosmetic ingredient in the practices of use and concentration as described in this report.

Comprehensive and comparative studies on nanocytotoxicity of glyceryl monooleate- and phytantriol-based lipid liquid crystalline nanoparticles.

BACKGROUND: Lipid liquid crystalline nanoparticles (LLCNPs) emerge as a suitable system for drug and contrast agent delivery. In this regard due to their unique properties, they offer a solubility of a variety of active pharmaceutics with different polarities increasing their stability and the possibility of controlled delivery. Nevertheless, the most crucial aspect underlying the application of LLCNPs for drug or contrast agent delivery is the unequivocal assessment of their biocompatibility, including cytotoxicity, genotoxicity, and related aspects. Although studies regarding the cytotoxicity of LLCNPs prepared from various lipids and surfactants were conducted, the actual mechanism and its impact on the cells (both cancer and normal) are not entirely comprehended. Therefore, in this study, LLCNPs colloidal formulations were prepared from two most popular structure-forming lipids, i.e., glyceryl monooleate (GMO) and phytantriol (PHT) with different lipid content of 2 and 20 w/w%, and the surfactant Pluronic F-127 using the top-down approach for further comparison of their properties. Prepared formulations were subjected to physicochemical characterization and followed with in-depth biological characterization, which included cyto- and genotoxicity towards cervical cancer cells (HeLa) and human fibroblast cells (MSU 1.1), the evaluation of cytoskeleton integrity, intracellular reactive oxygen species (ROS) generation upon treatment with prepared LLCNPs and finally the identification of internalization pathways. RESULTS: Results denote the higher cytotoxicity of PHT-based nanoparticles on both cell lines on monolayers as well as cellular spheroids, what is in accordance with evaluation of ROS activity level and cytoskeleton integrity. Detected level of ROS in cells upon the treatment with LLCNPs indicates their insignificant contribution to the cellular redox balance for most concentrations, however distinct for GMO- and PHT-based LLCNPs. The disintegration of cytoskeleton after administration of LLCNPs implies the relation between LLCNPs and F-actin filaments. Additionally, the expression of four genes involved in DNA damage and important metabolic processes was analyzed, indicating concentration-dependent differences between PHT- and GMO-based LLCNPs. CONCLUSIONS: Overall, GMO-based LLCNPs emerge as potentially more viable candidates for drug delivery systems as their impact on cells is not as deleterious as PHT-based as well as they were efficiently internalized by cell monolayers and 3D spheroids.

Dihydropyriculol produced by Pyricularia oryzae inhibits the growth of Streptomyces griseus.

Dihydropyriculol is a major secondary metabolite of Pyricularia oryzae. However, the biological activity of dihydropyriculol has not been reported. Here, we showed that dihydropyriculol has inhibitory activity against Streptomyces griseus. Localization analysis of dihydropyriculol revealed that dihydropyriculol could reach to S. griseus under confrontation culture. These results suggest that dihydropyriculol can be used as a chemical weapon against S. griseus.

Lipid membranes exposed to dispersions of phytantriol and monoolein cubosomes: Langmuir monolayer and HeLa cell membrane studies.

The interactions of liquid-crystalline nanoparticles based on lipid-like surfactants, glyceryl monooleate, monoolein (GMO) and 1,2,3-trihydroxy-3,7,11,15-tetramethylhexadecane, phytantriol (PT) with selected model lipid membranes prepared by Langmuir technique were compared. Monolayers of DPPC, DMPS and their mixture DPPC:DMPS 87:13 mol% were used as simple models of one leaflet of a cell membrane. The incorporation of cubosomes into the lipid layers spread at the air-water interface was followed by surface-pressure measurements and Brewster angle microscopy. The cubosome - membrane interactions lead to the fluidization of the model membranes but this effect depended on the composition of the model membrane and on the type of cubosomes. The interactions of PT cubosomes with lipid layers, especially DMPS-based monolayer were stronger compared with those of GMO-based nanoparticles. The kinetics of incorporation of cubosomal material into the lipid layer was influenced by the extent of hydration of the polar headgroups of the lipid: faster in the case of smaller, less hydrated polar groups of DMPS than for strongly hydrated uncharged choline of DPPC. The membrane disrupting effect of cubosomes increased at longer times of the lipid membrane exposure to the cubosome solution and at larger carrier concentrations. Langmuir monolayer observations correspond well to results of studies of HeLa cells exposed to cubosomes. The larger toxicity of PT cubosomes was confirmed by MTS. Their ability to disrupt lipid membranes was imaged by confocal microscopy. On the other hand, PT cubosomes easily penetrated cellular membranes and released cargo into various cellular compartments more effectively than GMO-based nanocarriers. Therefore, at low concentrations, they may be further investigated as a promising drug delivery tool.

High-Frequency Application of Cationic Agents Containing Lubricant Eye Drops Causes Cumulative Corneal Toxicity in an Ex Vivo Eye Irritation Test Model.

Purpose: High-frequency applied cetalkonium chloride (CAC) and benzalkonium chloride (BAC) 0.02% did not hamper corneal healing in a living rabbit model of induced corneal erosion. In contrast, the ex vivo eye irritation test (EVEIT) shows inhibition of healing for these substances. In a systematic ex vivo reproduction of the in vivo experiments, we discuss the background of these differences. Methods: Excised rabbit corneas (n = 5 per group) were cultured in artificial anterior chambers (EVEIT). Four erosions were induced for each cornea before starting regular 21 installations/day over 3 days of (1) CAC containing eye drops (Cationorm®), (2) 0.02% BAC. Corneal fluorescein staining, quantification of glucose-/lactate consumption, and histology were performed. Results: BAC 0.02% treated corneas showed increased epithelial lesions from 10.13 ± 0.65 mm2 to 10 ± 0.8 mm2 on day 0, to 86.82 ± 5.18 mm2 (P < 0.0001) by day 3. After a trend toward smaller lesions for CAC on day 1, erosion sizes increased significantly by day 3 from 9.82 ± 0.30 mm2 to 29.51 ± 16.87 mm2 (P < 0.05). For 1 cornea, corneal erosions nearly disappeared on day 3 (0.89 mm2). Corneal lactate increased significantly for BAC and CAC, whereas glucose concentrations were unchanged. Histology revealed disintegration of the corneal structures for both compounds. Conclusions: The data underline the EVEIT as a predictive toxicity test to show side effects in a time-compressed manner. The consistency of these predictions was previously demonstrated by the EVEIT for BAC, phosphate buffer, and others. The EVEIT is suited for a chronic application prediction of tolerability and toxic side effects of eye drops in particular, and other chemicals in general.

The effects of aliphatic alcohols and related acid metabolites in zebrafish embryos - correlations with rat developmental toxicity and with effects in advanced life stages in fish.

The zebrafish embryo toxicity test (ZFET) is a simple medium-throughput test to inform about (sub)acute lethal effects in embryos. Enhanced analysis through morphological and teratological scoring, and through gene expression analysis, detects developmental effects and the underlying toxicological pathways. Altogether, the ZFET may inform about hazard of chemical exposure for embryonal development in humans, as well as for lethal effects in juvenile and adult fish. In this study, we compared the effects within a series of 12 aliphatic alcohols and related carboxylic acid derivatives (ethanol, acetic acid, 2-methoxyethanol, 2-methoxyacetic acid, 2-butoxyethanol, 2-butoxyacetic acid, 2-hydroxyacetic acid, 2-ethylhexan-1-ol, 2-ethylhexanoic acid, valproic acid, 2-aminoethanol, 2-(2-hydroxyethylamino)ethanol) in ZFET and early life stage (ELS, 28d) exposures, and compared ZFET results with existing results of rat developmental studies and LC50s in adult fish. High correlation scores were observed between compound potencies in ZFET with either ELS, LC50 in fish and developmental toxicity in rats, indicating similar potency ranking among the models. Compounds could be mapped to specific pathways in an adverse outcome pathway (AOP) network through morphological scoring and gene expression analysis in ZFET. Similarity of morphological effects and gene expression profiles in pairs of alcohols with their acid metabolites suggested metabolic activation of the parent alcohols, although with additional, metabolite-independent activity independent for ethanol and 2-ethylhexanol. Overall, phenotypical and gene expression analysis with these compounds indicates that the ZFET can potentially contribute to the AOP for developmental effects in rodents, and to predict toxicity of acute and chronic exposure in advanced life stages in fish.

Ecotoxicity and interacting mechanism of anionic surfactant sodium dodecyl sulfate (SDS) and its mixtures with nonionic surfactant fatty alcohol-polyoxyethlene ether (AEO).

This paper reports the proportion-dependent toxicity of binary surfactant mixtures containing anionic sodium dodecyl sulfate (SDS) and nonionic fatty alcohol-polyoxyethlene ether (AEO) toward Photobacterium phosphoreum. The crucial role of toxicity interactions was elucidated by spectroscopic probing the refolding of the unfolded bovine serum albumin (BSA) induced by SDS and theoretical calculating the interaction parameter of mixed surfactants based on Rubingh's model from the critical micelle concentrations. The SDS/AEO mixtures can be divided into two groups based on the toxicity response to the proportion of AEO in the mixtures: Group I contained low mass proportions of AEO, that is, SDS:AEO = 4:1, 3:1; Group II featured high AEO proportions, that is, SDS:AEO = 3:2, 1:1, 2:3, 1:4. The toxicity of SDS/AEO mixtures decreased with the enhanced proportion of AEO in Group I and then fluctuated slightly when the AEO proportion increased to that of Group II. The mixture with the mass ratio of 1:1 showed a slightly higher toxicity than the others in Group II. Scanning electron microscopy (SEM) images illustrated that the addition of AEO hindered the action of SDS against the cell membrane. Fluorescence measurement indicated that AEO could extract SDS molecules embedded in the BSA matrix, except for those bound to the highly active sites of BSA, and refold stepwise the unfolded protein. The results were in excellent analogy to the proportion-dependent toxicity of SDS/AEO mixture, indicating the formation of mixed micelles playing a key role. The interaction parameter further revealed that antagonism led to the mixture with equal mass ratio (1:1) showing higher toxicity than other mass ratios in Group II. These results can be useful for compounding SDS/AEO mixtures in application efficiently and eco-friendly.

Steamed Ginger May Enhance Insulin Secretion through KATP Channel Closure in Pancreatic ß-Cells Potentially by Increasing 1-Dehydro-6-Gingerdione Content.

Ginger (Zingiber officinale Roscoe) and its active compounds (gingerols, shogaols and paradols) have been reported as having beneficial functions for several diseases, including diabetes. In this study, we revealed that the steaming process could enhance the anti-diabetic potential of ginger. To confirm the anti-diabetic effect of steamed ginger extract (GG03), we assessed pancreatic islets impaired by alloxan in zebrafish and demonstrated anti-hyperglycemic efficacy in a mouse model. The EC50 values of ginger extract (GE) and GG03 showed that the efficacy of GG03 was greater than that of GE. In addition, LC50 values demonstrated that GG03 had lower toxicity than GE, and the comparison of the Therapeutic Index (TI) proved that GG03 is a safer functional food. Furthermore, our data showed that GG03 significantly lowered hyperglycemia in a diabetic mouse model. HPLC was performed to confirm the change in the composition of steamed ginger. Interestingly, GG03 showed a 375% increase in 1-dehydro-6-gingerdione (GD) compared with GE. GD has not yet been studied much pharmacologically. Thus, we identified the protective effects of GD in the damaged pancreatic islets of diabetic zebrafish. We further assessed whether the anti-diabetic mechanism of action of GG03 and GD involves insulin secretion. Our results suggest that GG03 and GD might stimulate insulin secretion by the closure of KATP channels in pancreatic ß-cells.

Ecotoxicity and micellization behavior of anionic surfactant sodium dodecylbenzene sulfonate (SDBS) and its mixtures with nonionic surfactant fatty alcohol-polyoxyethylene ether (AEO).

Surfactant mixtures have extensive industrial applications due to their ideal properties and low ecotoxicity. However, the ecotoxicity of surfactant mixtures with different proportions and their correlation with surface properties have remained poorly investigated. In this study, the ecotoxicity and surface activity of the composites of anionic surfactant sodium dodecylbenzene sulfonate (SDBS) and nonionic surfactant fatty alcohol-polyoxyethylene ether (AEO) in various mass ratios were assessed, and the correlation between ideal application properties and safe ecological perspective of the composites was explored. The ecotoxicity of individual SDBS, AEO, and SDBS/AEO mixtures was determined using the bioluminescence inhibition assay with Photobacterium phosphoreum, and the critical micelle concentrations (CMC) were measured by surface tension method and steady-state fluorescence spectroscopy. Sodium dodecylbenzene sulfonate (SDBS) showed a considerably higher toxicity than individual AEO and SDBS/AEO mixtures. Scanning electron microscope images illustrated the rupture of bacteria membrane induced by SDBS, and the addition of AEO alleviated the damage. According to the dose-response relationship on luminous bacteria, SDBS/AEO mixtures were divided into three groups (group I with a high proportion of SDBS, SDBS:AEO = 4:1 and 3:2; group II, SDBS:AEO = 1:1; group III with a high proportion of AEO, SDBS:AEO = 2:3 and 1:4). The sequence of toxicity of the SDBS/AEO mixtures was group II > group III > group I, demonstrating that the toxicity of the composites was related to the mixture proportion instead of the amount of AEO added. The CMC order of SDBS/AEO mixtures was group II > group I > group III, and it was proportion dependent. Furthermore, ΔCM was defined as the difference of the experimental (CM) and ideal CMC (CMideal) of the mixed system, indicating the interaction between the two kinds of surfactants. The order of the ΔCM was group II > group III > group I, which was consistent with the sequence of the toxicity. Therefore, ΔCM can be a potential indicator for the hazardous assessment of surfactant mixtures involving high ionic strength.