-
Bioorganic Chemistry Jun 2024Hyperpigmentation disorders may result from inappropriate melanin deposition and/or excessive melanin synthesis. They are classified mainly as aesthetic problems, but...
Hyperpigmentation disorders may result from inappropriate melanin deposition and/or excessive melanin synthesis. They are classified mainly as aesthetic problems, but they can significantly affect human health by decreasing self-esteem. There are available only limited treatment options for hyperpigmentation disorder, among others, cosmetic products applied topically. Depigmenting ingredients were found to be ineffective and characterized by various side effects. As a result, many efforts are made to discover novel, potent, and safe melanogenesis inhibitors for possible use in topical cosmetic depigmenting formulations. Cinnamic acid derivatives constitute a widely tested group for that purpose. This article reports research in the group of N-alkyl cinnamamide derivatives (un)substituted in phenyl ring. Among tested series, (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide (compound 21) showed the most promising inhibitory properties in mushroom tyrosinase assay (IC = 36.98 ± 1.07 µM for monophenolase activity, IC = 146.71 ± 16.82 µM for diphenolase activity) and melanin production inhibition in B16F10 mouse melanoma cell line at concentration 6.25 µM resulting probably from decreasing of Tyr, Mitf, Tyrp-1, and Tyrp-2 genes expression. This compound also showed melanin production inhibitory properties in pigmented reconstructed human epidermis when used in 1 % and 2 % solutions in 50 % PEG400. In vitro evaluation of its safety profile showed no cytotoxicity to human keratinocytes HaCaT, human skin fibroblasts BJ, and human primary epidermal melanocytes HEMa, no mutagenicity in the Ames test, no genotoxicity in micronucleus test, no phototoxicity, as well as no skin irritation potential tested in PEG400 solution. This compound was also shown to penetrate across the epidermis to reach the possible site of action. The performed research led to classify (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide as a novel potential depigmenting cosmetic ingredient.
PubMed: 38878750
DOI: 10.1016/j.bioorg.2024.107533 -
Computers in Biology and Medicine Jun 2024Non-sugar sweeteners (NSSs) or artificial sweeteners have long been used as food chemicals since World War II. NSSs, however, also raise a concern about their...
Non-sugar sweeteners (NSSs) or artificial sweeteners have long been used as food chemicals since World War II. NSSs, however, also raise a concern about their mutagenicity. Evaluating the mutagenic ability of NSSs is crucial for food safety; this step is needed for every new chemical registration in the food and pharmaceutical industries. A computational assessment provides less time, money, and involved animals than the in vivo experiments; thus, this study developed a novel computational method from an ensemble convolutional deep neural network and read-across algorithms, called DeepRA, to classify the mutagenicity of chemicals. The mutagenicity data were obtained from the curated Ames test data set. The DeepRA model was developed using both molecular descriptors and molecular fingerprints. The obtained DeepRA model provides accurate and reliable mutagenicity classification through an independent test set. This model was then used to examine the NSSs-related chemicals, enabling the evaluation of mutagenicity from the NSSs-like substances. Finally, this model was publicly available at https://github.com/taraponglab/deepra for further use in chemical regulation and risk assessment.
PubMed: 38870727
DOI: 10.1016/j.compbiomed.2024.108731 -
Journal of Toxicology and Environmental... Sep 2024is one of the most predominant freshwater bloom-forming cyanobacterium found globally which is capable of producing toxic secondary metabolites including microcystins...
is one of the most predominant freshwater bloom-forming cyanobacterium found globally which is capable of producing toxic secondary metabolites including microcystins that might intoxicate animals and humans when contaminated water or food is ingested. Aubl is one of the plants that might possess bioactive compounds capable of controlling growth and reproduction of . The present study aimed to determine the presence of bioactive compounds in extracts and determine alterations occurred in growth and reproduction of when exposed to these plant extracts. In addition, this investigation aimed to examine the influence of on antioxidant enzymes detected in . The results obtained demonstrated that the aqueous and ethanolic extracts of presented potential for control of cyanobacteria populations, exhibiting algicidal action on as well as interfering in antioxidant enzymes activities and parameters associated with oxidative stress. Phytochemical analyses demonstrated the presence of polyphenols and flavonoids content in both extracts. In addition, application of extracts did not produce cytogenotoxicity and/or mutagenicity utilizing test. Therefore, further studies are needed in order to identify and characterize the compounds responsible for these effects on and provide information regarding the possible application of in the treatment of drinking water.
Topics: Microcystis; Plant Extracts; Antioxidants; Oxidative Stress
PubMed: 38865103
DOI: 10.1080/15287394.2024.2366320 -
Food Chemistry Jun 2024The natural vanilla market, which generates millions annually, is predominantly dependent on Vanilla planifolia, a species characterized by low genetic variability and...
The natural vanilla market, which generates millions annually, is predominantly dependent on Vanilla planifolia, a species characterized by low genetic variability and susceptibility to pathogens. There is an increasing demand for natural vanilla, prized for its complex, authentic, and superior quality compared to artificial counterparts. Therefore, there is a necessity for innovative production alternatives to ensure a consistent and stable supply of vanilla flavors. In this context, vanilla crop wild relatives (WRs) emerge as promising natural sources of the spice. However, these novel species must undergo toxicity assessments to evaluate potential risks and ensure safety for consumption. This study aimed to assess the non-mutagenic and non-carcinogenic properties of ethanolic extracts from V. bahiana, V. chamissonis, V. cribbiana, and V. planifolia through integrated metabolomic profiling, in vitro toxicity assays, and in silico analyses. The integrated approach of metabolomics, in vitro assays, and in silico analyses has highlighted the need for further safety assessments of Vanilla cribbiana ethanolic extract. While the extracts of V. bahiana, V. chamissonis, and V. planifolia generally demonstrated non-mutagenic properties in the Ames assay, V. cribbiana exhibited mutagenicity at high concentrations (5000 μg/plate) in the TA98 strain without metabolic activation. This finding, coupled with the dose-dependent cytotoxicity observed in WST-1 (Water Soluble Tetrazolium) assays, a colorimetric method that assesses the viability of cells exposed to a test substance, underscores the importance of concentration in the safety evaluation of these extracts. Kaempferol and pyrogallol, identified with higher intensity in V. cribbiana, are potential candidates for in vitro mutagenicity. Although the results are not conclusive, they suggest the safety of these extracts at low concentrations. This study emphasizes the value of an integrated approach in providing a nuanced understanding of the safety profiles of natural products, advocating for cautious use and further research into V. cribbiana mutagenicity.
PubMed: 38852444
DOI: 10.1016/j.foodchem.2024.139948 -
Journal of Hazardous Materials Aug 2024Titanium dioxide nanoparticles (nTiO) have been considered a possible carcinogen to humans, but most existing studies have overlooked the role of human enzymes in...
Titanium dioxide nanoparticles (nTiO) have been considered a possible carcinogen to humans, but most existing studies have overlooked the role of human enzymes in assessing the genotoxicity of nTiO. Here, a toxicogenomics-based in vitro genotoxicity assay using a GFP-fused yeast reporter library was employed to elucidate the genotoxic potential and mechanisms of nTiO. Moreover, two new GFP-fused yeast reporter libraries containing either human CYP1A1 or CYP1A2 genes were constructed by transformation to investigate the potential modulation of nTiO genotoxicity in the presence of human CYP enzymes. This study found a lack of appreciable nTiO genotoxicity as indicated by the yeast reporter library in the absence of CYP expression but a significantly elevated indication of genotoxicity in either CYP1A1- or CYP1A2-expressing yeast. The intracellular reactive oxygen species (ROS) measurement indicated significantly higher ROS in yeast expressing either enzyme. The detected mitochondrial DNA damage suggested mitochondria as one of the target sites for oxidative damage by nTiO in the presence of either one of the CYP enzymes. The results thus indicated that the genotoxicity of nTiO was enhanced by human CYP1A1 or CYP1A2 enzyme and was associated with elevated oxidative stress, which suggested that the similar mechanisms could occur in human cells.
Topics: Humans; Titanium; Reactive Oxygen Species; Saccharomyces cerevisiae; Cytochrome P-450 CYP1A1; DNA Damage; Mutagenicity Tests; Cytochrome P-450 CYP1A2; Mutagens; Oxidative Stress; Genes, Reporter; Nanoparticles; Metal Nanoparticles; Green Fluorescent Proteins
PubMed: 38850947
DOI: 10.1016/j.jhazmat.2024.134850 -
Scientific Reports Jun 2024As patient exposure to ionizing radiation from medical imaging and its risks are continuing issues, this study aimed to evaluate DNA damage and repair markers after...
As patient exposure to ionizing radiation from medical imaging and its risks are continuing issues, this study aimed to evaluate DNA damage and repair markers after myocardial perfusion single-photon emission computed tomography (MPS). Thirty-two patients undergoing Tc-99m sestamibi MPS were studied. Peripheral blood was collected before radiotracer injection at rest and 60-90 min after injection. The comet assay (single-cell gel electrophoresis) was performed with peripheral blood cells to detect DNA strand breaks. Three descriptors were evaluated: the percentage of DNA in the comet tail, tail length, and tail moment (the product of DNA tail percentage and tail length). Quantitative PCR (qPCR) was performed to evaluate the expression of five genes related to signaling pathways in response to DNA damage and repair (ATM, ATR, BRCA1, CDKN1A, and XPC). Mann-Whitney's test was employed for statistical analysis; p < 0.05 was considered significant. Mean Tc-99m sestamibi dose was 15.1 mCi. After radiotracer injection, comparing post-exposure to pre-exposure samples of each of the 32 patients, no statistically significant differences of the DNA percentage in the tail, tail length or tail moment were found. qPCR revealed increased expression of BRCA1 and XPC, without any significant difference regarding the other genes. No significant increase in DNA strand breaks was detected after a single radiotracer injection for MPS. There was activation of only two repair genes, which may indicate that, in the current patient sample, the effects of ionizing radiation on the DNA were not large enough to trigger intense repair responses, suggesting the absence of significant DNA damage.
Topics: Humans; Female; DNA Damage; Male; Tomography, Emission-Computed, Single-Photon; DNA Repair; Middle Aged; Aged; Technetium Tc 99m Sestamibi; Myocardial Perfusion Imaging; BRCA1 Protein; Comet Assay
PubMed: 38844507
DOI: 10.1038/s41598-024-63537-3 -
Pakistan Journal of Biological Sciences... Apr 2024<b>Background and Objective:</b> Gamma irradiation induces genotoxicity, characterized by the formation of extra-nuclear bodies and left behind during the...
<b>Background and Objective:</b> Gamma irradiation induces genotoxicity, characterized by the formation of extra-nuclear bodies and left behind during the anaphase stage of cell division, often referred to as a micronucleus (MN). The present work aims to monitor exposure to ionizing radiation as a genotoxic agent in the lymphocytes of workers at radiation energy centers. <b>Materials and Methods:</b> The lymphocyte cytokinesis block micronucleus assay used and analyzed the correlation between the Nuclear Division Index (NDI), age, blood type and the number of micronuclei (MN). Blood samples were collected from 20 volunteers in heparin tubes, exposed to 2 Gy gamma rays and cultured <i>in vitro</i>. <b>Results:</b> A significant difference in the number of micronuclei between blood group A and blood groups A, B and AB. The Nuclear Division Index (NDI) value for lymphocytes of radiation energy center workers after gamma radiation was significant (1.74±0.1) but still within the normal range. Neither MN frequency nor NDI values correlated with age, but MN frequency showed a correlation with blood type. <b>Conclusion:</b> The gamma irradiation did not induce a cytostatic effect but proved genotoxic to the lymphocytes of radiation energy center workers. Notably, blood type A demonstrated higher sensitivity to gamma radiation.
Topics: Humans; Gamma Rays; Lymphocytes; Micronucleus Tests; Cytokinesis; Occupational Exposure; Adult; Male; Middle Aged; Micronuclei, Chromosome-Defective; Female
PubMed: 38840468
DOI: 10.3923/pjbs.2024.276.282 -
Food Chemistry May 2024Laccase mediators possess advantage of oxidizing substrates with high redox potentials, such as aflatoxin B (AFB). High costs of chemically synthesized mediators limit...
Laccase mediators possess advantage of oxidizing substrates with high redox potentials, such as aflatoxin B (AFB). High costs of chemically synthesized mediators limit laccase industrial application. In this study, thin stillage extract (TSE), a byproduct of corn-based ethanol fermentation was investigated as the potential natural mediator of laccases. Ferulic acid, p-coumaric acid, and vanillic acid were identified as the predominant phenolic compounds of TSE. With the assistance of 0.05 mM TSE, AFB degradation activity of novel laccase Glac1 increased by 17 times. The promoting efficiency of TSE was similar to ferulic acid, but superior to vanillic acid and p-coumaric acid, with 1.2- and 1.3-fold increases, respectively. After Glac1-TSE treatment, two oxidation products were identified. Ames test showed AFB degradation products lost mutagenicity. Meanwhile, TSE also showed 1.3-3.0 times promoting effect on laccase degradation activity in cereal flours. Collectively, a safe and highly efficient natural mediator was obtained for aflatoxin detoxification.
PubMed: 38833866
DOI: 10.1016/j.foodchem.2024.139862 -
Journal of Toxicology and Environmental... Sep 2024The aviation sector is believed to be responsible for considerable environmental damage attributed to emission of a large number and amount of pollutants. Airports are...
The aviation sector is believed to be responsible for considerable environmental damage attributed to emission of a large number and amount of pollutants. Airports are often surrounded by forest fragments and humid areas that attract birds of prey and hence may potentially serve as useful bioindicators. The aim of the present study was to examine genotoxic potential in raptors exposed to airport pollution using the micronucleus (MN) test and morphological changes as evidenced by bilateral symmetry. This investigation was conducted at Salgado Filho International Airport of Porto Alegre - RS as well as in private and zoological breeding grounds. The presence of metals was measured in the blood cells of the collected birds. Seventeen birds () were used in this study 11 from exposed and 6 from non-exposed group. The nuclear alterations clearly indicate that organisms exposed to airport pollution exhibited a significantly higher frequency of genetic damage compared to non-exposed birds. Further, manganese and chromium were detected exclusively in the blood of the exposed group. In contrast, the analysis of bilateral symmetry did not detect any significant morphologic differences between the two groups. Therefore, data indicate that blood genotoxic stress occurs in birds of prey living in civil aviation areas as evidenced by MN frequency increase and presence of manganese and chromium.
Topics: Animals; Micronucleus Tests; Brazil; Airports; Environmental Monitoring; Micronuclei, Chromosome-Defective; DNA Damage; Cell Nucleus; Raptors; Male
PubMed: 38828979
DOI: 10.1080/15287394.2024.2361247 -
Chemico-biological Interactions Jul 2024Tris(2-butoxyethyl) phosphate (TBOEP) is an organophosphorus flame retardant ubiquitously present in the environment and even the human body. TBOEP is toxic in multiple...
Tris(2-butoxyethyl) phosphate (TBOEP) is an organophosphorus flame retardant ubiquitously present in the environment and even the human body. TBOEP is toxic in multiple tissues, which forms dealkylated and hydroxylated metabolites under incubation with human hepatic microsomes; however, the impact of TBOEP metabolism on its toxicity, particularly mutagenicity (typically requiring metabolic activation), is left unidentified. In this study, the mutagenicity of TBOEP in human hepatoma cell lines (HepG2 and C3A) and the role of specific CYPs were studied. Through molecular docking, TBOEP bound to human CYP1A1, 1B1, 2B6 and 3A4 with energies and conformations favorable for catalyzing reactions, while the conformations of its binding with human CYP1A2 and 2E1 appeared unfavorable. In C3A cells (endogenous CYPs being substantial), TBOEP exposing for 72 h (2-cell cycle) at low micromolar levels induced micronucleus, which was abolished by 1-aminobenzotriazole (inhibitor of CYPs); in HepG2 cells (CYPs being insufficient) TBOEP did not induce micronucleus, whose effect was however potentiated by pretreating the cells with PCB126 (CYP1A1 inducer) or rifampicin (CYP3A4 inducer). TBOEP induced micronucleus in Chinese hamster V79-derived cell lines genetically engineered for stably expressing human CYP1A1 and 3A4, but not in cells expressing the other CYPs. In C3A cells, TBOEP selectively induced centromere protein B-free micronucleus (visualized by immunofluorescence) and PIG-A gene mutations, and elevated γ-H2AX rather than p-H3 (by Western blot) which indicated specific double-strand DNA breaks. Therefore, this study suggests that TBOEP may induce DNA/chromosome breaks and gene mutations in human cells, which requires metabolic activation by CYPs, primarily CYP1A1 and 3A4.
Topics: Animals; Humans; Flame Retardants; Molecular Docking Simulation; Cricetinae; Cytochrome P-450 Enzyme System; Mutagens; Organophosphorus Compounds; Cricetulus; Organophosphates; Hep G2 Cells; Micronucleus Tests
PubMed: 38823534
DOI: 10.1016/j.cbi.2024.111088