Health & Environmental Research Online (HERO)


Malonates (108-58-8 & 105-53-3)


175 References Were Found:

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Ammonia role in glial dysfunction in methylmalonic acidemia

Authors: Gabbi, P; Nogueira, V; Haupental, F; Rodrigues, FS; Do Nascimento, PS; Barbosa, S; Arend, J; Furian, AF; Oliveira, MS; Dos Santos, ARS; Royes, LFF; Fighera, MR (2018) Toxicology Letters 295:237-248. HERO ID: 4733654

[Less] Hyperammonemia is a common finding in patients with methylmalonic acidemia. However, its contribution . . . [More] Hyperammonemia is a common finding in patients with methylmalonic acidemia. However, its contribution to methylmalonate (MMA)-induced neurotoxicity is poorly understood. The aim of this study was evaluate whether an acute metabolic damage to brain during the neonatal period may disrupt cerebral development, leading to neurodevelopmental disorders, as memory deficit. Mice received a single intracerebroventricular dose of MMA and/or NH4Cl, administered 12 hs after birth. The maze tests showed that MMA and NH4Cl injected animals (21 and 40 days old) exhibited deficit in the working memory test, but not in the reference memory test. Furthermore, MMA and NH4Cl increased the levels of 2',7'-dichlorofluorescein-diacetate (DCF), TNF-α, IL-1β in the cortex, hippocampus and striatum of mice. MMA and NH4Cl also increased glial proliferation in all structures. Since the treatment of MMA and ammonia increased cytokines levels, we suggested that it might be a consequence of the glial activation induced by the acid and ammonia, leading to delay in the developing brain and contributing to behavioral alterations. However, this hypothesis is speculative in nature and more studies are needed to clarify this possibility.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

RIFM fragrance ingredient safety assessment, diethyl malonate, CAS Registry Number 105-53-3

Authors: Api, AM; Belsito, D; Botelho, D; Bruze, M; Burton, GA; Buschmann, J; Dagli, ML; Date, M; Dekant, W; Deodhar, C; Francis, M; Fryer, AD; Jones, L; Joshi, K; La Cava, S; Lapczynski, A; Liebler, DC; O'Brien, D; Patel, A; Penning, TM; Ritacco, G; Romine, J; Sadekar, N; Salvito, D; Schultz, TW; Sipes, IG; Sullivan, G; Thakkar, Y; Tokura, Y; Tsang, S (2018) Food and Chemical Toxicology. HERO ID: 4923458

[Less] Summary: The use of this material under current conditions is supported by existing information. The . . . [More] Summary: The use of this material under current conditions is supported by existing information.

The material diethyl malonate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Target data show that diethyl malonate is not genotoxic. The repeated dose and reproductive toxicity endpoints were completed using dimethyl malonate (CAS# 108-59-8) as a read-across analog, which provided an MOE > 100. Data from target material and read-across analog, pentanedioic acid, 1,5-dimethyl ester (CAS# 1119-40-0) show that is material is not a concern for skin sensitization. The local respiratory toxicity endpoint was completed using the TTC (Threshold of Toxicological Concern) for a Cramer Class I material (1.4 mg/day). The phototoxicity/photoallergenicity endpoint was completed based on UV spectra. The environmental endpoints were evaluated; diethyl malonate was found not to be a PBT as per the IFRA Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., PEC/PNEC) are < 1.

Technical Report
Technical Report

Substance information: Diethyl malonate

Author: ECHA (2018) Helsinki, Finland: European Chemicals Agency. [Fact Sheet] HERO ID: 4939813

[Less] This substance is manufactured and/or imported in the European Economic Area in 1 000+ tonnes per year. This . . . [More] This substance is manufactured and/or imported in the European Economic Area in 1 000+ tonnes per year.

This substance is used by consumers, in articles, by professional workers (widespread uses), in formulation or re-packing, at industrial sites and in manufacturing.

Technical Report
Technical Report

G04: In vivo micronucleus summary data. Test substance: dimethyl adipate. CAS Number: 627-93-0.

Author: National Toxicology Program (NTP) (2018) (A86146). HERO ID: 5097600


Technical Report
Technical Report

G04: In vivo micronucleus summary data. Test substance: dimethyl glutarate. CAS Number: 1119-40-0.

Author: National Toxicology Program (NTP) (2018) (A36863). HERO ID: 5097601


The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

DNA binding, artificial nuclease activity and cytotoxic studies of newly synthesized steroidal pyrimidines

Authors: Dar, AM; Rah, B; Mir, S; Nabi, R; Shamsuzzaman, R; Gatoo, MA; Mashrai, A; Khan, Y (2018) International Journal of Biological Macromolecules 111:52-61. HERO ID: 4923443

[Less] The new steroidal pyrimidine derivatives (4-6) were synthesized by the reaction of steroidal thiosemicarbazones . . . [More] The new steroidal pyrimidine derivatives (4-6) were synthesized by the reaction of steroidal thiosemicarbazones with (2-methyl) diethyl malonate in absolute ethanol. After characterization by spectral and analytical data, the DNA interaction studies of compounds (4-6) were carried out by UV-vis, fluorescence spectroscopy, hydrodynamic measurements, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.31×103M-1, 1.93×103M-1 and 2.05×103M-1, respectively indicating the higher binding affinity of compound 4 towards DNA. Gel electrophoresis demonstrated that compound 4 showed a strong interaction during the concentration dependent cleavage activity with pBR322 DNA. The molecular docking study suggested the intercalation of steroidal pyrimidine moiety in the minor groove of DNA. During in vitro cytotoxicity, compounds (4-6) revealed potential toxicity against the different human cancer cells (MTT assay). During DAPI staining, the nuclear fragmentations on cells occurred after treatment with compounds 4 and 5. Western blotting analysis clearly indicates that compound 4 causes apoptosis in MCF-7 cancer cells. The results revealed that compound 4 has better prospectus to act as a cancer chemotherapeutic candidate, which warrants further in vivo anticancer investigations.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Succinate induces synovial angiogenesis in rheumatoid arthritis through metabolic remodeling and HIF-1α/VEGF axis

Authors: Li, Y; Liu, Y; Wang, C; Xia, WR; Zheng, JY; Yang, J; Liu, B; Liu, JQ; Liu, LF (2018) Free Radical Biology and Medicine 126:1-14. HERO ID: 4923445

[Less] BACKGROUND AND PURPOSE: In response to hypoxic succinate accumulates in arthritis synovium, . . . [More] BACKGROUND AND PURPOSE: In response to hypoxic succinate accumulates in arthritis synovium, however, the implication is little known. This study aims to investigate whether succinate could act as a metabolic signal linking metabolic alternation with angiogenesis in arthritis synovium.

EXPERIMENTAL APPROACH: The interaction between elevated succinate and VEGF production was examined in endothelial cells. Succinate production, HIF-1α induction and angiogenesis in the hypoxic synovium of collagen-induced arthritis rats were also investigated.

KEY RESULTS: Intracellular succinate promoted VEGF production and induced angiogenic response dependent on HIF-1α induction in endothelial cells. Luciferase reporter assay showed that succinate increased VEGF expression through gene promoter activation dependent on HIF-1α induction. Intracellular succinate released into intercellular space, where extracellular succinate activated succinate receptor G-protein-coupled receptor 91 (GPR91) and induced VEGF production, further exacerbating angiogenesis. In addition, TGF-β1 treatment increased succinate production due to the reversal of succinate dehydrogenase (SDH) activation, and consistently, SDH inhibitor dimethyl malonate reduced angiogenesis in the arthritis synovium.

CONCLUSION AND IMPLICATIONS: More than an intermediate, succinate functioned as a signaling molecule to link metabolic reprograming with angiogenesis. Intracellular succinate induced angiogenesis through HIF-1α induction, while extracellular succinate acted on GPR91 activation, working together to disturb energy metabolism and exacerbate inflammation and angiogenesis in arthritis synovium. Our work suggested that suppression of SDH could prevent succinate accumulation and inhibit angiogenesis via blocking HIF-1α/VEGF axis. This finding not only provides a novel insight into angiogenesis, but also reveals a potential therapeutical strategy to attenuate revascularization in arthritis.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Biosynthesis of angelyl-CoA in Saccharomyces cerevisiae

Authors: Callari, R; Fischer, D; Heider, H; Weber, N (2018) Microbial Cell Factories 17:72. HERO ID: 4923449

[Less] BACKGROUND: The angelic acid moiety represents an essential modification in many biologically . . . [More] BACKGROUND: The angelic acid moiety represents an essential modification in many biologically active products. These products are commonly known as angelates and several studies have demonstrated their therapeutic benefits, including anti-inflammatory and anti-cancer effects. However, their availability for use in the development of therapeutics is limited due to poor extraction yields. Chemical synthesis has been achieved but its complexity prevents application, therefore microbial production may offer a promising alternative. Here, we engineered the budding yeast Saccharomyces cerevisiae to produce angelyl-CoA, the CoA-activated form of angelic acid.

RESULTS: For yeast-based production of angelyl-CoA we first expressed genes recently identified in the biosynthetic cluster ssf of Streptomyces sp. SF2575 in S. cerevisiae. Exogenous feeding of propionate and heterologous expression of a propionyl-CoA synthase from Streptomyces sp. were initially employed to increase the intracellular propionyl-CoA level, resulting in production of angelyl-CoA in the order of 5 mg/L. Substituting the Streptomyces sp. propionyl-CoA carboxylase with a carboxylase derived from Streptomyces coelicolor resulted in angelyl-CoA levels up to 6.4 mg/L. In vivo analysis allowed identification of important intermediates in the pathway, including methyl-malonyl-CoA and 3-hydroxyl-2-methyl-butyryl-CoA. Furthermore, methyl-malonate supplementation and expression of matB CoA ligase from S. coelicolor allowed for methyl-malonyl-CoA synthesis and supported, together with parts of the ssf pathway, angelyl-CoA titres of approximately 1.5 mg/L. Finally, feeding of angelic acid to yeasts expressing acyl-CoA ligases from plant species led to angelyl-CoA production rates of approximately 40 mg/L.

CONCLUSIONS: Our results demonstrate the biosynthesis of angelyl-CoA in yeast from exogenously supplied carboxylic acid precursors. This is the first report on the activity of the ssf genes. We envision that our approach will provide a platform for a more sustainable production of the pharmaceutically important compound class of angelates.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Inhibiting succinate dehydrogenase by dimethyl malonate alleviates brain damage in a rat model of cardiac arrest

Authors: Xu, J; Pan, H; Xie, X; Zhang, J; Wang, Y; Yang, G (2018) Neuroscience 393:24-32. HERO ID: 4923454

[Less] Brain damage is a leading cause of death in patients with cardiac arrest (CA). The accumulation of succinate . . . [More] Brain damage is a leading cause of death in patients with cardiac arrest (CA). The accumulation of succinate during ischemia by succinate dehydrogenase (SDH) is an important mechanism of ischemia-reperfusion injury. It was unclear whether inhibiting the oxidation of accumulated succinate could also mitigate brain damage after CA. In this study, rats were subjected to a 6 min of CA, and cardiopulmonary resuscitation (CPR) was performed with administration of normal saline or dimethyl malonate (DMM, a competitive inhibitor of SDH). After the return of spontaneous circulation, neurological function of the rats was assessed by a tape removal test for 3 days. The rats were then sacrificed, and their brains were used to assess neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Hippocampal tissues were used for Western blotting analysis and biochemical detection. In addition, hippocampal mitochondria during CA and CPR were isolated. The relative mitochondrial membrane potential (MMP) and cytochrome C in the cytosol were detected. Our results show that DMM promoted ROSC and neurological performance in rats after CA. The TUNEL assay showed that DMM reduced neuronal apoptosis. Western blotting analysis showed that DMM inhibited the activation of caspase-3 and enhanced the expression of HIF-1α. Moreover, DMM inhibited excessive hyperpolarization of MMP after CPR, and prevented the release of cytochrome C. Therefore, inhibiting SDH by DMM alleviated brain damage after CA, and the main mechanisms included inhibiting the excessive hyperpolarization of MMP, reducing the generation of mtROS and stabilizing the structure of HIF-1α.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Chemical warfare agent simulants for human volunteer trials of emergency decontamination: A systematic review

Authors: James, T; Wyke, S; Marczylo, T; Collins, S; Gaulton, T; Foxall, K; Amlôt, R; Duarte-Davidson, R (2018) Journal of Applied Toxicology 38:113-121. [Review] HERO ID: 4923473

[Less] Incidents involving the release of chemical agents can pose significant risks to public health. In such . . . [More] Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining non-toxic at the dose applied. This review focuses on studies that employed chemical warfare agent simulants in decontamination contexts, to identify those simulants most suitable for use in HVTs of emergency decontamination. Twenty-two simulants were identified, of which 17 were determined unsuitable for use in HVTs. The remaining simulants (n = 5) were further scrutinized for potential suitability according to toxicity, physicochemical properties and similarities to their equivalent toxic counterparts. Three suitable simulants, for use in HVTs were identified; methyl salicylate (simulant for sulphur mustard), diethyl malonate (simulant for soman) and malathion (simulant for VX or toxic industrial chemicals). All have been safely used in previous HVTs, and have a range of physicochemical properties that would allow useful inference to more toxic chemicals when employed in future studies of emergency decontamination systems.