Arsenic-containing Hydrocarbons Research Articles

Exploring the Effect of Arsenic-Containing Hydrocarbon on the Bidirectional Synaptic Plasticity of the Dorsal Hippocampus.

Arsenic-containing hydrocarbons (AsHCs) are common in marine organisms. However, there is little research on their effects on the central nervous system's advanced activities, such as cognition. Bidirectional synaptic plasticity dynamically regulates cognition through the balance of long-term potentiation (LTP) and long-term depression (LTD). However, the effects of AsHCs on bidirectional synaptic plasticity and the underlying molecular mechanisms remain unexplored. This study provides the first evidence that 15 μg As L-1 AsHC 360 enhances bidirectional synaptic plasticity, occurring during the maintenance phase rather than the baseline phase. Further calcium gradient experiments hypothesize that AsHC 360 may enhance bidirectional synaptic plasticity by affecting calcium ion levels. The enhancement of bidirectional synaptic plasticity by 15 μg As L-1 AsHC 360 holds significant implications in improving cognitive function, treating neuro-psychiatric disorders, promoting neural recovery, and enhancing brain adaptability.

Speciation analysis and toxicity evaluation of arsenolipids-an overview focusing on sea food.

Arsenic, which can be divided into inorganic and organic arsenic, is a toxic metalloid that has been identified as a human carcinogen. A common source of arsenic exposure in seafood is arsenolipid, which is a complex structure of lipid-soluble organic arsenic compounds. At present, the known arsenolipid species mainly include arsenic-containing fatty acids (AsFAs), arsenic-containing hydrocarbons (AsHCs), arsenic glycophospholipids (AsPLs), and cationic trimethyl fatty alcohols (TMAsFOHs). Furthermore, the toxicity between different species is unique. However, the mechanism underlying arsenolipid toxicity and anabolism remain unclear, as arsenolipids exhibit a complex structure, are present at low quantities, and are difficult to extract and detect. Therefore, the objective of this overview is to summarize the latest research progress on methods to evaluate the toxicity and analyze the main speciation of arsenolipids in seafood. In addition, novel insights are provided to further elucidate the speciation, toxicity, and anabolism of arsenolipids and assess the risks on human health.

AsHC 360 Exposure Influence on Epileptiform Discharges in Hippocampus of Infantile Male Rats In Vitro

Arsenic-containing hydrocarbons (AsHCs) are typical arsenolipids found in various marine organisms. They can penetrate the blood–brain barrier, specifically affecting synaptic plasticity and the learning and memory ability of hippocampal neurons. Temporal lobe epilepsy often occurs in the hippocampus. Thus, the possible influence of AsHCs exposure to temporal lobe epilepsy garnered attention. The present study investigated the effects of epileptiform discharges (EDs) signals introduced by low-magnesium ACSF in the hippocampus of infantile male rats in vitro, using electrophysiological techniques with multi-electrode arrays under AsHC 360 exposure. In our study of the effects of AsHC 360 on EDs signals, we found that inter-ictal discharges (IIDs) were not significantly impacted. When AsHC 360 was removed, any minor effects observed were reversed. However, when we examined the impact of AsHC 360 on ictal discharges (IDs), distinct patterns emerged based on the concentration levels. For low-concentration groups (5, 20, 60 μg As L−1), both the frequency and duration effects on IDs returned to normal post-elimination of AsHC 360. However, this recovery was not evident for concentrations of 100 μg As L−1 or higher. IDs were only observed in EDs signals during exposures to AsHC 360 concentrations up to 60 μg As L−1. In these conditions, ID frequencies significantly enhanced with the increased of AsHC 360 concentration. At high concentrations of AsHC 360 (≥100 μg As L−1), the transition from IIDs or pre-ictal discharges (PIDs) to IDs was notably inhibited. Additional study on co-exposure of AsHC 360 (100 μg As L−1) and agonist (10 nM (S)-(-)-Bay-K-8644) indicated that the regulation of EDs signals under AsHC 360 exposure could be due to directly interference with the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) expression which influences the binding of excitatory glutamate neurotransmitter to AMPAR. The results suggest that EDs activities in the hippocampus of infantile Sprague Dawley rats are concentration-dependent on AsHC 360 exposure. Thus, it provides a basis for the seafood intake with AsHCs for epileptic patients and those with potential seizures.

Evaluation of the effects of three arsenolipids on liver damage based on element imbalance and oxidative damage

AbstractThe International Agency for Research on Cancer has classified semimetal arsenic as a human carcinogen. Arsenic poisoning can severely impact human health. Arsenic can be classified into inorganic and organic arsenic, with arsenolipids (AsLs) belonging to the category of organic arsenic. The primary species of AsLs include arsenic‐containing hydrocarbons (AsHCs), fatty acids, and phospholipids. AsLs are highly abundant in marine organisms and diet may be the primary source of exposure to AsLs. Although increasing evidence shows that AsLs are cytotoxic to humans, the specific toxicity and its mechanism remain unclear. This study aimed to evaluate the hepatotoxicity and possible mechanisms of the toxic effects of AsLs in mice. Three AsLs (AsHC 332, AsHC 346, and AsHC 374) were administered via gavage at a dose of 3 mg/kg for 4 weeks. The results showed that short‐term exposure did not affect the normal growth and development of mice. However, it caused liver damage in mice, mainly by disrupting the metabolism of selenium, copper, zinc, and other elements related to the synthesis of antioxidant enzymes, thereby reducing the activity of antioxidant enzymes and the expression of related genes. The liver damage effect of AsHC 332 was the strongest among the three AsLs.

Quantitative analysis of arsenic containing hydrocarbons in marine samples by GC-MS

Environmental context The marine ecosystem is highly elevated in arsenic in comparison to the terrestrial environment. More than 100 different naturally occurring organoarsenic compounds have been found in different marine organisms. In order to understand how highly toxic AsHCs are formed and bioaccumulate in different marine organisms, large scale monitoring of AsHCs from a range of different laboratories is necessary. Despite their toxicity, AsHCs have not been extensively studied due in part to the lack of low-cost analytical methods and the lack of commercially available standards.Rational This study aims to develop a new analytical method for the quantitative determination of arsenic-containing hydrocarbons (AsHCs) with gas chromatography–mass spectrometry (GC-MS). The new method is an alternative approach to determine these compounds in environmental samples.Methodology AsHCs were extracted and purified from fish oil and seaweed samples. Due to the thermal conversion of oxo-AsHCs to their trivalent forms in the injection port of the GC, the conversion is incomplete resulting in low signal intensities and large carry overs. We therefore chemically reduced AsHCs to their trivalent forms and analysed them with GC-MS, gas chromatography–tandem mass spectrometry (GC-MS/MS) and high performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC-ICPMS). The possibility for compound independent quantification with commercially available standards was investigated.Results After optimisation of conditions for reduction of AsHCs, these compounds could be determined in marine samples using authentic standards with the new method. Results showed good agreement with results from HPLC-ICPMS. The novel GC-MS method showed compound independent quantification using triphenylarsine (TPA) as a commercially available standard.Discussion With the developed method we could demonstrate the applicability of GC-MS for the quantitative determination of AsHCs in marine samples for the first time. The compound independent quantification with TPA opens up a quantification for AsHCs species for which no standards are commercially available. The broad applicability might enhance screening for these toxic compounds in the environment.

Arsenolipids in raw and cooked seafood products in southwest China: A non-targeted analysis

Arsenolipids are the primary form of arsenic in the fat of marine organisms. Because seafood is a common source of arsenic exposure and some arsenolipids are toxic, studying the abundance and species of arsenolipids in seafood is crucial for health risk assessment. Current arsenolipid research is confined by analytical techniques and limited to raw seafood analysis, despite the fact that most seafood is ingested cooked. Therefore, the aim of this study is to evaluate which seafood contributes to arsenolipid dietary intake and investigate the changes in arsenolipids before and after cooking. In Chongqing, China, popular seafood such as clam, shrimp, oyster, abalone, hairtail, and yellow croaker were collected. The raw and cooked samples prepared from these seafood products were examined using a non-targeted screening approach established for arsenolipids, which coupled high-performance liquid chromatography with data-independent high-resolution quadrupole-time-of-flight electrospray ionization tandem mass spectrometry. Arsenic-containing hydrocarbons (AsHC330, AsHC332, and AsHC360), arsenic-containing fatty acids (AsFA362, AsFA390, AsFA404, AsFA418, and AsFA422), trimethylarsine oxide, and thiolated trimethylarsinic acid were detected. The species of arsenolipids in each type of seafood remained intact after heating in the microwave oven. In cooked samples, the concentrations of AsFA362 and AsFA390 were significantly lower than in raw samples, whereas the concentrations of other arsenolipids were unchanged. Microwave cooking did not result in the thiolation of the detected arsenolipids. The most detected species in raw and cooked samples were AsFA362, AsFA390, and AsFA418. Most arsenolipid species were found in the highest levels in hairtails and yellow croakers. It is the first time that arsenolipids have been found in the oyster, abalone, abalone liver, and yellow croaker. The present study contributes to a better understanding of arsenolipids exposure from seafood, which is useful for assessing the health risks of arsenic.

Effect of arsenic-containing hydrocarbon on the long-term potentiation at Schaffer Collateral-CA1 synapses from infantile male rat

Arsenic-containing hydrocarbons (AsHCs) are common constituents of marine organisms and have potential toxicity to human health. This work is to study the effect of AsHCs on long-term potentiation (LTP) for the first time. A multi-electrode array (MEA) system was used to record the field excitatory postsynaptic potential (fEPSP) of CA1 before and after treatment with AsHC 360 in hippocampal slices from infantile male rats. The element content of Na, K, Ca, Mg, Mn, Cu, Zn, and As in the hippocampal slices were analyzed by elemental mass spectrometry after the neurophysiological experiment. The results showed that low AsHC 360 (1.5 μg As L−1) had no effect on the LTP, moderate AsHC 360 (3.75−15 μg As L−1) enhanced the LTP, and high AsHC 360 (45−150 μg As L−1) inhibited the LTP. The enhancement of the LTP by promoting Ca2+ influx was proved by a Ca2+ gradient experiment. The inhibition of the LTP was likely due to damage of synaptic cell membrane integrity. This study on the neurotoxicity of AsHCs showed that high concentrations have a strong toxic effect on the LTP in hippocampus slices of the infantile male rat, which may lead to a negative effect on the development, learning, and memory.

Arsenolipids in Plankton from High- and Low-Nutrient Oceanic Waters Along a Transect in the North Atlantic.

Although the natural occurrence of arsenic-containing lipids (arsenolipids) in marine organisms is now well established, the possible role of these unusual compounds in organisms and in the cycling of arsenic in marine systems remains largely unexplored. We report the finding of arsenolipids in 61 plankton samples collected from surface marine waters of high- and low-nutrient content along a transect spanning the Gulf Stream in the North Atlantic Ocean. Using high-performance liquid chromatography (HPLC) coupled to both elemental and molecular mass spectrometry, we show that all 61 plankton samples contained six identifiable arsenolipids, namely, three arsenosugar phospholipids (AsPL958, 10-13%; AsPL978, 13-25%; and AsPL1006, 7-10% of total arsenolipids), two arsenic-containing hydrocarbons (AsHC332, 4-10% and AsHC360, 1-2%), and a methoxy-sugar arsenolipid that contained phytol (AsSugPhytol, 1-3%). The relative amounts of the six arsenolipids showed clear dependence on the nutrient status of the ambient water with plankton collected from high-nutrient waters having less of the arsenosugar phospholipids and more of the three non-P containing arsenolipids compared to low-nutrient waters. By combining these first field data of arsenolipids in plankton with reported global phytoplankton productivity, we estimate that the oceans' phytoplankton transform per year 50 000-100 000 tons of arsenic into arsenolipids.

Discovery and Identification of Arsenolipids Using a Precursor-Finder Strategy and Data-Independent Mass Spectrometry.

Arsenolipids are a class of lipid-soluble arsenic species. They are present in seafoods and show high potentials of cytotoxicity and neurotoxicity. Hindered by traditional low-throughput analytical techniques, the characterization of arsenolipids is far from complete. Here, we report on a sensitive and high-throughput screening method for arsenolipids in krill oil, tuna fillets, hairtail heads, and kelp. We demonstrate the detection and identification of 23 arsenolipids, including novel arsenic-containing fatty acids (AsFAs), hydroxylated AsFAs, arsenic-containing hydrocarbons (AsHCs), hydroxylated AsHCs, thiolated trimethylarsinic acids, and arsenic-containing lysophosphatidylcholines not previously reported. The new method incorporated precursor ion scan (PIS) into data-independent acquisition. High-performance liquid chromatography (HPLC) electrospray ionization quadrupole time-of-flight mass spectrometry (ESI–qToF–MS) was used to perform the sequential window acquisition of all theoretical spectra (SWATH). Comprehensive HPLC–MS and MS/MS data were further processed using a fragment-guided chromatographic computational program Precursorfinder developed here. Precursorfinder achieved efficient peak-picking, retention time comparison, hierarchical clustering, and wavelet coherence calculations to assemble fragment features with their target precursors. The identification of arsenolipids was supported by coeluting the HPLC–MS peaks detected with the characteristic fragments of arsenolipids. Method validation using available arsenic standards and the successful identification of previously unknown arsenolipids in seafood samples demonstrated the applicability of the method for environmental research.

Cellular toxicological characterization of a thioxolated arsenic-containing hydrocarbon

Arsenolipids, especially arsenic-containing hydrocarbons (AsHC), are an emerging class of seafood originating contaminants. Here we toxicologically characterize a recently identified oxo-AsHC 332 metabolite, thioxo-AsHC 348 in cultured human liver (HepG2) cells. Compared to results of previous studies of the parent compound oxo-AsHC 332, thioxo-AsHC 348 substantially affected cell viability in the same concentration range but exerted about 10-fold lower cellular bioavailability. Similar to oxo-AsHC 332, thioxo-AsHC 348 did not substantially induce oxidative stress nor DNA damage. Moreover, in contrast to oxo-AsHC 332 mitochondria seem not to be a primary subcellular toxicity target for thioxo-AsHC 348. This study indicates that thioxo-AsHC 348 is at least as toxic as its parent compound oxo-AsHC 332 but very likely acts via a different mode of toxic action, which still needs to be identified.

Toxicity of three types of arsenolipids: species-specific effects in Caenorhabditis elegans.

Although fish and seafood are well known for their nutritional benefits, they contain contaminants that might affect human health. Organic lipid-soluble arsenic species, so called arsenolipids, belong to the emerging contaminants in these food items; their toxicity has yet to be systematically studied. Here, we apply the in vivo model Caenorhabditis elegans to assess the effects of two arsenic-containing hydrocarbons (AsHC), a saturated arsenic-containing fatty acid (AsFA), and an arsenic-containing triacylglyceride (AsTAG) in a whole organism. Although all arsenolipids were highly bioavailable in Caenorhabditis elegans, only the AsHCs were substantially metabolized to thioxylated or shortened metabolic products and induced significant toxicity, affecting both survival and development. Furthermore, the AsHCs were several fold more potent as compared to the toxic reference arsenite. This study clearly indicates the need for a full hazard identification of subclasses of arsenolipids to assess whether they pose a risk to human health.

Variation in arsenolipid concentrations in seafood consumed in Japan

Variation in arsenolipid concentrations was assessed in 18 seafood samples including fish, shellfish, and crustaceans purchased in Japan. Analyses were performed by high performance liquid chromatography-inductively coupled plasma mass spectrometry/electrospray ionization tandem mass spectrometry. Stable isotope ratios for nitrogen and carbon were also measured in the samples for obtaining trophic level information of the species. Arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) were detected in the seafood samples; the toxic AsHCs were found in all of the seafood samples with large variation in the concentrations (83 ± 73 ng As/g fw, coefficient of variation = 88%). Our previous point estimate of health risk of AsHCs intake via seafood consumption in Japan, based on average AsHC concentration in seafood, suggested insignificant risk, and the present study supports our previous estimate. AsHC concentrations significantly correlated with lipid content of the seafood samples (r = 0.67, p < 0.01), a result expected because of the fat solubility of the compounds. The AsHCs concentrations, however, were not significantly correlated with nitrogen stable isotope ratios suggesting that AsHCs do not biomagnify. The source of the observed large variation in AsHC concentrations will be the subject of further investigation.

Origin of arsenolipids in sediments from Great Salt Lake

Environmental contextArsenic is a globally distributed element, occurring in various chemical forms with toxicities ranging from harmless to highly toxic. We examined sediment samples from Great Salt Lake, an extreme salt environment, and found a variety of organoarsenic species not previously recorded in nature. These new compounds are valuable pieces in the puzzle of how organisms detoxify arsenic, and in our understanding of the global arsenic cycle. AbstractArsenic-containing lipids are natural products found predominantly in marine organisms. Here, we report the detection of known and new arsenolipids in sediment samples from Great Salt Lake, a hypersaline lake in Utah, USA, using high-performance liquid chromatography in combination with both elemental and molecular mass spectrometry. Sediments from four investigated sites contained appreciable quantities of arsenolipids (22–312ng As g−1 sediment) comprising several arsenic-containing hydrocarbons and 20 new compounds shown to be analogues of phytyl 2-O-methyl dimethylarsinoyl riboside. We discuss potential sources of the detected arsenolipids and find a phytoplanktonic origin most plausible in these algal detritus-rich salt lake sediments.

Estimation of daily intake of arsenolipids in Japan based on a market basket survey

Arsenolipid concentrations were measured in 17 food composites prepared from 152 food items purchased in Shizuoka city, Japan, to (1) determine the food contributing to daily intake of arsenolipids, and (2) estimate the daily intake of arsenolipids. Analysis of arsenolipids was performed by high performance liquid chromatography-inductively coupled plasma mass spectrometry/electrospray ionization tandem mass spectrometry (HPLC-ICP-MS/ESI-MS-MS). Arsenic containing hydrocarbons (AsHCs), arsenic containing fatty acids (AsFAs), and arsenosugar phospholipids (AsSugPLs) were detected only in “algae” and “fish and shellfish” of the 17 food composites in a concentration range of 4.4–233 ng As/g fresh weight (fw). Two cytotoxic arsenolipids, AsHC332 and AsHC360, were detected in “algae” and “fish and shellfish” in the concentrations range of 33–40 ng As/g fw. The estimated average daily intake of AsHC332 and AsHC360 was ca 3000 and 360 ng As/person/day, or 50 and 6.0 ng As/kg bw/day, respectively. The present study indicated that arsenolipids from “algae” and “fish and shellfish” consumption contributed to the daily intake of toxic AsHCs, though the margin of exposure for the AsHC332 and AsHC360 does not appear to pose a health risk for the general Japanese population.

Arsenic-containing hydrocarbons: effects on gene expression, epigenetics, and biotransformation in HepG2 cells.

Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsHCs (AsHC 332 and AsHC 360) on the expression of 44 genes covering DNA repair, stress response, cell death, autophagy, and epigenetics via RT-qPCR in human liver (HepG2) cells. Both AsHCs affected the gene expression, but to different extents. After treatment with AsHC 360, flap structure-specific endonuclease 1 (FEN1) as well as xeroderma pigmentosum group A complementing protein (XPA) and (cytosine-5)-methyltransferase 3A (DNMT3A) showed time- and concentration-dependent alterations in gene expression, thereby indicating an impact on genomic stability. In the subsequent analysis of epigenetic markers, within 72h, neither AsHC 332 nor AsHC 360 showed an impact on the global DNA methylation level, whereas incubation with AsHC 360 increased the global DNA hydroxymethylation level. Analysis of cell extracts and cell media by HPLC-mass spectrometry revealed that both AsHCs were considerably biotransformed. The identified metabolites include not only the respective thioxo-analogs of the two AsHCs, but also several arsenic-containing fatty acids and fatty alcohols, contributing to our knowledge of biotransformation mechanisms of arsenolipids.

Arsenic-containing hydrocarbons disrupt a model in vitro blood-cerebrospinal fluid barrier

Lipid-soluble arsenicals, so-called arsenolipids, have gained a lot of attention in the last few years because of their presence in many seafoods and reports showing substantial cytotoxicity emanating from arsenic-containing hydrocarbons (AsHCs), a prominent subgroup of the arsenolipids. More recent in vivo and in vitro studies indicate that some arsenolipids might have adverse effects on brain health.In the present study, we focused on the effects of selected arsenolipids and three representative metabolites on the blood-cerebrospinal fluid barrier (B-CSF-B), a brain-regulating interface. For this purpose, we incubated an in vitro model of the B-CSF-B composed of porcine choroid plexus epithelial cells (PCPECs) with three AsHCs, two arsenic-containing fatty acids (AsFAs) and three representative arsenolipid metabolites (dimethylarsinic acid, thio/oxo-dimethylpropanoic acid) to examine their cytotoxic potential and impact on barrier integrity. The toxic arsenic species arsenite was also tested in this way and served as a reference substance. While AsFAs and the metabolites showed no cytotoxic effects in the conducted assays, AsHCs showed a strong cytotoxicity, being up to 1.5-fold more cytotoxic than arsenite. Analysis of the in vitro B-CSF-B integrity showed a concentration-dependent disruption of the barrier within 72 h. The correlation with the decreased plasma membrane surface area (measured as capacitance) indicates cytotoxic effects. These findings suggest exposure to elevated levels of certain arsenolipids may have detrimental consequences for the central nervous system.

Effects of arsenolipids on in vitro blood-brain barrier model.

Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids (AsLs) occurring in fish and edible algae, possess a substantial neurotoxic potential in fully differentiated human brain cells. Previous in vivo studies indicating that AsHCs cross the blood-brain barrier of the fruit fly Drosophila melanogaster raised the question whether AsLs could also cross the vertebrate blood-brain barrier (BBB). In the present study, we investigated the impact of several representatives of AsLs (AsHC 332, AsHC 360, AsHC 444, and two arsenic-containing fatty acids, AsFA 362 and AsFA 388) as well as of their metabolites (thio/oxo-dimethylpropionic acid, dimethylarsinic acid) on porcine brain capillary endothelial cells (PBCECs, in vitro model for the blood-brain barrier). AsHCs exerted the strongest cytotoxic effects of all investigated arsenicals as they were up to fivefold more potent than the toxic reference species arsenite (iAsIII). In our in vitro BBB-model, we observed a slight transfer of AsHC 332 across the BBB after 6h at concentrations that do not affect the barrier integrity. Furthermore, incubation with AsHCs for 72h led to a disruption of the barrier at sub-cytotoxic concentrations. The subsequent immunocytochemical staining of three tight junction proteins revealed a significant impact on the cell membrane. Because AsHCs enhance the permeability of the in vitro blood-brain barrier, a similar behavior in an in vivo system cannot be excluded. Consequently, AsHCs might facilitate the transfer of accompanying foodborne toxicants into the brain.

Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons.

Arsenolipids are lipid-soluble organoarsenic compounds, mainly occurring in marine organisms, with arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) representing two major subgroups. Recently, toxicity studies of several arsenolipids showed a high cytotoxic potential of those arsenolipids in human liver and bladder cells. Furthermore, feeding studies with Drosophila melanogaster indicated an accumulation of arsenolipids in the fruit fly's brain. In this study, the neurotoxic potential of three AsHCs, two AsFAs and three metabolites (dimethylarsinic acid, thio/oxo-dimethylarsenopropanoic acid) was investigated in comparison to the toxic reference arsenite (iAsIII) in fully differentiated human brain cells (LUHMES cells). Thereby, in the case of AsHCs both the cell number and cell viability were reduced in a low micromolar concentration range comparable to iAsIII, while AsFAs and the applied metabolites were less toxic. Mechanistic studies revealed that AsHCs reduced the mitochondrial membrane potential, whereas neither iAsIII nor AsFAs had an impact. Furthermore, neurotoxic mechanisms were investigated by examining the neuronal network. Here, AsHCs massively disturbed the neuronal network and induced apoptotic effects, while iAsIII and AsFAs showed comparatively lesser effects. Taking into account the substantial in vitro neurotoxic potential of the AsHCs and the fact that they could transfer across the physiological barriers of the brain, a neurotoxic potential in vivo for the AsHCs cannot be excluded and needs to be urgently characterized.

Arsenolipids exert less toxicity in a human neuron astrocyte co-culture as compared to the respective monocultures.

Arsenic-containing hydrocarbons (AsHCs), natural products found in seafood, have recently been shown to exert toxic effects in human neurons. In this study we assessed the toxicity of three AsHCs in cultured human astrocytes. Due to the high cellular accessibility and substantial toxicity observed astrocytes were identified as further potential brain target cells for arsenolipids. Thereby, the AsHCs exerted a 5-19-fold higher cytotoxicity in astrocytes as compared to arsenite. Next we compared the toxicity of the arsenicals in a co-culture model of the respective human astrocytes and neurons. Notably the AsHCs did not show any substantial toxic effects in the co-culture, while arsenite did. The arsenic accessibility studies indicated that in the co-culture astrocytes protect neurons against cellular arsenic accumulation especially after incubation with arsenolipids. In summary, these data underline the importance of the glial-neuron interaction when assessing the in vitro neurotoxicity of new unclassified metal species.

Imaging by Elemental and Molecular Mass Spectrometry Reveals the Uptake of an Arsenolipid in the Brain of Drosophila melanogaster.

Arsenic-containing lipids (arsenolipids) are natural products of marine organisms such as fish, invertebrates, and algae, many of which are important seafoods. A major group of arsenolipids, namely, the arsenic-containing hydrocarbons (AsHC), have recently been shown to be cytotoxic to human liver and bladder cells, a result that has stimulated interest in the chemistry and toxicology of these compounds. In this study, elemental laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) and molecular matrix-assisted laser desorption/ionization (MALDI-)MS were used to image and quantify the uptake of an AsHC in the model organism Drosophila melanogaster. Using these two complementary methods, both an enrichment of arsenic and the presence of the AsHC in the brain were revealed, indicating that the intact arsenolipid had crossed the blood-brain barrier. Simultaneous acquisition of quantitative elemental concentrations and molecular distributions could allow new insight into organ-specific enrichment and possible transportation processes of arsenic-containing bioactive compounds in living organisms.