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Oxidative Medicine and Cellular... 2018Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form... (Review)
Review
Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P). Recently, a novel role of FTY720 as a potential anticancer drug has emerged. One of the anticancer mechanisms of FTY720 involves the induction of reactive oxygen species (ROS) and subsequent apoptosis, which is largely independent of its property as an S1P modulator. ROS have been considered as a double-edged sword in tumor initiation/progression. Intriguingly, prooxidant therapies have attracted much attention due to its efficacy in cancer treatment. These strategies include diverse chemotherapeutic agents and molecular targeted drugs such as sulfasalazine which inhibits the CD44v-xCT (cystine transporter) axis. In this review, we introduce our recent discoveries using a chemical genomics approach to uncover a signaling network relevant to FTY720-mediated ROS signaling and apoptosis, thereby proposing new potential targets for combination therapy as a means to enhance the antitumor efficacy of FTY720 as a ROS generator. We extend our knowledge by summarizing various measures targeting the vulnerability of cancer cells' defense mechanisms against oxidative stress. Future directions that may lead to the best use of FTY720 and ROS-targeted strategies as a promising cancer treatment are also discussed.
Topics: Animals; Antineoplastic Agents; Apoptosis; Humans; Immunosuppressive Agents; Organophosphates; Reactive Oxygen Species; Sphingosine
PubMed: 29785244
DOI: 10.1155/2018/4397159 -
Biomedica : Revista Del Instituto... Jun 2023Introduction. Dengue is a public health problem in La Guajira region. Control has focused on the vector using insecticides, including organophosphates. Objective. To...
Introduction. Dengue is a public health problem in La Guajira region. Control has focused on the vector using insecticides, including organophosphates. Objective. To evaluate the state of susceptibility to organophosphates insecticides in fifteen Aedes aegypti (L.) populations in La Guajira, Colombia. Materials and methods. We collected samples of third-instar larvae and adult mosquitoes of Ae. aegypti in the municipalities of Albania, Barrancas, Dibulla, Distracción, El Molino, Fonseca, Hatonuevo, La Jagua del Pilar, Maicao, Manaure, Riohacha, San Juan del Cesar, Uribia, Urumita, Villanueva. Bioassays for temefos, malathion, and pirimiphos-methyl were carried out following the methodology of the World Health Organization, and the bottle technique using the guidance of the Centers for Disease Control and Prevention. Susceptibility to temefos was determined through the resistance ratio between lethal concentration 50 and lethal concentration 95; for the compounds temefos, malathion and pirimiphos-methyl, susceptibility was calculated using diagnostic dose and diagnostic time in the populations evaluated. Rockefeller susceptible strain was used as a control. Results: All evaluated populations of Ae. aegypti from La Guajira were found to be susceptible to temefos (ratio resistance to CL50<5.0; ratio resistance to CL95<5.0; 98 - 100 % mortality); pirimiphosmethyl (99 - 100 % mortality), and malathion (100 % mortality). Conclusion. Based on the results, the use of temefos, malathion, and pirimiphosmethyl is feasible for the control of Ae. aegypti in the evaluated populations.
Topics: United States; Animals; Aedes; Organophosphates; Colombia; Temefos; Mosquito Vectors
PubMed: 37433166
DOI: 10.7705/biomedica.6677 -
Chemical Research in Toxicology Jun 2020Isopropylated and -butylated triarylphosphate esters (ITPs and TBPPs, respectively) are plasticizers and flame retardants that are ubiquitous in indoor environments;...
Isopropylated and -butylated triarylphosphate esters (ITPs and TBPPs, respectively) are plasticizers and flame retardants that are ubiquitous in indoor environments; however, no studies to date have characterized their metabolism. Using human liver subcellular S9 fractions, phase I and II metabolism of triphenyl phosphate (TPHP), 4--butylphenyl diphenyl phosphate (4tBPDPP), 2-isopropylphenyl diphenyl phosphate (2IPPDPP), and 4-isopropylphenyl diphenyl phosphate (4IPPDPP) was investigated at 1 and 10 μM doses. Parent depletion and the formation of known or suspected metabolites (e.g., likely hydrolysis or hydroxylated products), including diphenyl phosphate (DPHP), hydroxyl-triphenyl phosphate (OH-TPHP), isopropylphenyl phenyl phosphate (ip-PPP), and -butylphenyl phenyl phosphate (tb-PPP), were monitored and quantified via GC/MS or LC-MS/MS. tb-PPP and its conjugates were identified as the major metabolites of 4tBPDPP and accounted for 71% and 49%, respectively, of the parent molecule that was metabolized during the incubation. While the mass balance between parents and metabolites was conserved for TPHP and 4tBPDPP, approximately 20% of the initial parent mass was unaccounted for after quantifying suspected metabolites of 2IPPDPP and 4IPPDPP that had authentic standards available. Two novel ITP metabolites, mono-isopropenylphenyl diphenyl phosphate and hydroxy-isopropylphenyl diphenyl phosphate, were tentatively identified by high-resolution mass spectrometry and screened for in recently collected human urine where mono-isopropenylphenyl diphenyl phosphate was detected in one of nine samples analyzed. This study provides insight into the biological fate of ITP and TBPP isomers in human tissues and is useful in identifying appropriate biomarkers of exposure to monitor, particularly in support of epidemiological studies.
Topics: Biotransformation; Child; Child, Preschool; Environmental Pollutants; Esters; Flame Retardants; Humans; Liver; Organophosphates; Plasticizers; Subcellular Fractions
PubMed: 32129605
DOI: 10.1021/acs.chemrestox.0c00002 -
Chemosphere Sep 2021Dust serves as a strong sink for indoor pollutants, such as organophosphorus flame retardants (OPFRs). OPFRs are semivolatile chemicals that are slow in emissions but...
Dust serves as a strong sink for indoor pollutants, such as organophosphorus flame retardants (OPFRs). OPFRs are semivolatile chemicals that are slow in emissions but have long-term effects in indoor environments. This research studied the emission, sorption, and migration of OPFRs tris(2-chloroethyl) phosphate, tris(1-chloro-2-propyl) phosphate, and tris(1,3-dichloro-2-propyl) phosphate, from different sources to settled dust on OPFR source surfaces and OPFR-free surfaces. Four sink effect tests and six dust-source migration tests, including direct contact and sorption tests were conducted in 53 L stainless steel small chambers at 23 °C and 50% relative humidity. OPFR emission concentrations, and sorption and migration rates were determined. The dust-air and dust-material partition coefficients were estimated based on the experimental data and compared with those from the literature obtained by empirical equations. They are in the range of 1.4 × 10 to 2.6 × 10 (dimensionless) for the dust-air equilibrium partition coefficients and 2.38 × 10 to 0.8 (dimensionless) for the dust-material equilibrium partition coefficients. It was observed that the dust with less organic content and smaller size tended to absorb more OPFRs, but different dust did not significantly affect OPFRs emission from the same source to the chamber air. The dust-air partition favored the less volatile OPFRs in the house dust, whereas the emission from the source favored the volatile chemicals. Volatility of the chemicals had much less effect on dust-source partitioning than on dust-air partitioning. The results from this work improve our understating of the fate and mass transfer mechanisms between OPFRs sources, indoor air, surface, and dust.
Topics: Air Pollution, Indoor; Dust; Flame Retardants; Organophosphates; Organophosphorus Compounds; Phosphates
PubMed: 33839398
DOI: 10.1016/j.chemosphere.2021.130415 -
Toxicological Sciences : An Official... May 2021Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications...
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect during pregnancy. We measured 12 PFASs and four urinary OPFR metabolites in 132 healthy pregnant women during mid-gestation and examined a subset with biomarkers of placental development and disease (n = 62). Molecular biomarkers included integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and matrix metalloproteinase-1 (MMP1). Morphological endpoints included potential indicators of placental stress and the extent of cytotrophoblast (CTB)-mediated uterine artery remodeling. Serum PFASs and urinary OPFR metabolites were detected in ∼50%-100% of samples. The most prevalent PFASs were perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), with geometric mean (GM) levels of ∼1.3-2.8 (95% confidence limits from 1.2-3.1) ng/ml compared to ≤0.5 ng/ml for other PFASs. Diphenyl phosphate (DPhP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the most prevalent OPFR metabolites, with GMs of 2.9 (95% CI: 2.5-3.4) and 3.6 (95% CI: 2.2-3.1) ng/ml, respectively, compared to <1 ng/ml for bis(2-chloroethyl) phosphate (BCEP) and bis(1-chloro-2-propyl) phosphate (BCIPP). We found inverse associations of PFASs or OPFRs with ITGA1 or CDH5 immunoreactivity and positive associations with indicators of placental stress in multiple basal plate regions, indicating these chemicals may contribute to abnormal placentation and future health risks. Associations with blood pressure and lipid concentrations warrant further examination. This is the first study of these chemicals with placental biomarkers measured directly in human tissues and suggests specific biomarkers are sensitive indicators of exposure during a vulnerable developmental period.
Topics: Biomarkers; Female; Flame Retardants; Humans; Organophosphates; Placenta; Placentation; Pregnancy
PubMed: 33677611
DOI: 10.1093/toxsci/kfab028 -
Ecotoxicology and Environmental Safety Aug 2022Organophosphate flame retardants (OPFRs) are alternatives to brominated flame retardants (BFRs) and have recently gained wide acceptance in various materials. For the...
Organophosphate flame retardants (OPFRs) are alternatives to brominated flame retardants (BFRs) and have recently gained wide acceptance in various materials. For the treatment and prevention of diseases, it is also important to clarify the relationship between OPFRs and tumors, despite the fact that OPFRs are less toxic than BFRs. This research used the TCGA and CTD databases for transcriptome profiling and identifying OPFRs-related genes. GO and KEGG analyses suggested that OPFRs may be closely related to colorectal cancer (CRC), and genes correlated with OPFRs were significantly and differently expressed between tumor and normal group. Further, OPFRs-related genes were associated with a good prognosis in CRC patients. The deeper research demonstrated that one of the OPFRs-triphenyl phosphate could significantly increased the viability and proliferation of CRC cell lines compared with the control group. In addition, Our research also found that melatonin at 50 μM could significantly impact CRC cell proliferation and migration ability induced by TPP.
Topics: Cell Line; Colorectal Neoplasms; Flame Retardants; Humans; Organophosphates; Organophosphorus Compounds
PubMed: 36068737
DOI: 10.1016/j.ecoenv.2022.113778 -
Environment International Jan 2021The ubiquity of organophosphate esters (OPEs) in various environmental matrices inevitably pose human exposure risks. Numerous studies have investigated human exposure... (Review)
Review
The ubiquity of organophosphate esters (OPEs) in various environmental matrices inevitably pose human exposure risks. Numerous studies have investigated human exposure pathways to OPEs, including air inhalation, dust ingestion, dermal contact, and dietary and drinking water intake, and have indicated that indoor dust and indoor air routes are frequently the two main human exposure pathways. This article reviews the literature on OPE contamination in indoor air and dust from various microenvironments and on OPE particle size distributions and bioavailability in dust conducted over the past 10 years. Ways in which sampling strategies are related to the uncertainty of exposure assessment results and comparability among different studies in terms of sampling tools, sampling sites, and sample types are addressed. Also, the associations of OPEs in indoor dust/air with human biological samples were summarized. Studies on two emerging matrices, hand wipes and silicone wristbands, are demonstrated to be more comprehensive and accurate in reflecting personal human exposure to OPEs in microenvironments and are summarized. Given the direct application of some diester OPEs (di-OPEs) in numerous products, research on their existence in indoor dust and food and on their effects on human urine are also discussed. Finally, related research trends and avenues for future research are prospected.
Topics: Air Pollution, Indoor; China; Dust; Environmental Exposure; Environmental Monitoring; Esters; Flame Retardants; Humans; Organophosphates; Silicones
PubMed: 33395927
DOI: 10.1016/j.envint.2020.106261 -
Environment International Oct 2020Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) is a halogen-containing organophosphorus chemical that is widely employed in various consumer products with a high... (Review)
Review
Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) is a halogen-containing organophosphorus chemical that is widely employed in various consumer products with a high production volume. As an additive flame retardant (FR), TDCPP tends to be released into the environment through multiple routes. It is ubiquitous in environmental media, biotic matrixes, and humans, and thus is deemed to be an emerging environmental contaminant. To date, significant levels of TDCPP and its primary diester metabolite, bis(1,3-dichloro-2-propyl)phosphate, have been detected in human samples of seminal plasma, breast milk, blood plasma, placenta, and urine, thereby causing wide concern about the potential human health effects resulting from exposure to this chemical. Despite the progress in research on TDCPP over the past few years, we are still far from fully understanding the environmental behavior and health risks of this emerging contaminant. Thus, this paper critically reviews the environmental occurrence, exposure, and risks posed by TDCPP to organisms and human health among the literature published in the last decade. It has been demonstrated that TDCPP induces acute-, nerve-, developmental-, reproductive-, hepatic-, nephron-, and endocrine-disrupting toxicity in animals, which has caused increasing concern worldwide. Simultaneously, TDCPP induces cytotoxicity by increasing the formation of reactive oxygen species and inducing endoplasmic reticulum stress in multiple human cell lines in vitro, and also causes endocrine-disrupting effects, including reproductive dysfunction and adverse pregnancy outcomes, according to human epidemiology studies. This review not only provides a better understanding of the behavior of this emerging contaminant in the environment, but also enhances the comprehension of the health risks posed by TDCPP exposure to ecosystems and humans.
Topics: Animals; Ecosystem; Female; Flame Retardants; Humans; Organophosphates; Organophosphorus Compounds; Phosphates
PubMed: 32663715
DOI: 10.1016/j.envint.2020.105946 -
IARC Monographs on the Evaluation of... 1999
Topics: Animals; Carcinogenicity Tests; Carcinogens; Flame Retardants; Humans; Mutagenicity Tests; Mutagens; Neoplasms, Experimental; Organophosphates; Salmonella typhimurium
PubMed: 10476442
DOI: No ID Found -
Environmental Pollution (Barking, Essex... Apr 2024Organophosphate triesters (tri-OPEs) have found substantial use as plasticizers and flame retardants in commercial and industrial products. Despite upcoming potential... (Review)
Review
Organophosphate triesters (tri-OPEs) have found substantial use as plasticizers and flame retardants in commercial and industrial products. Despite upcoming potential restrictions on use of OPEs, widespread environmental contamination is likely for the foreseeable future. Organophosphate diesters (di-OPEs) are known biotic or abiotic degradation products of tri-OPEs. In addition, direct use of di-OPEs as commercial products also contributes to their presence in the atmosphere. We review the available data on contamination with tri-OPEs and di-OPEs in both indoor and outdoor air. Concentrations of tri-OPEs in indoor air exceed those in outdoor air. The widespread discovery of tri-OPE traces in polar regions and oceans is noteworthy and is evidence that they undergo long-range transport. There are only two studies on di-OPEs in outdoor air and no studies on di-OPEs in indoor air until now. Current research on di-OPEs in indoor and outdoor air is urgently needed, especially in countries with potentially high exposure to di-OPEs such as the UK and the US. Di-OPE concentrations are higher at e-waste dismantling areas than at surrounding area. We also summarise the methods employed for sampling and analysis of OPEs in the atmosphere and assess the relative contribution to atmospheric concentrations of di-OPEs made by environmental degradation of triesters, compared to the presence of diesters as by-products in commercial triester products. Finally, we identify shortcomings of current research and provide suggestions for future research.
Topics: Organophosphates; Environmental Exposure; Environmental Monitoring; Flame Retardants; Atmosphere; Esters; China
PubMed: 38402940
DOI: 10.1016/j.envpol.2024.123653