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Toxins, Volume 10, Issue 1 (January 2018)

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Cover Story (view full-size image) The peptide toxin ShK highlights the potential of sea anemones to produce valuable therapeutic [...] Read more.
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Open AccessReview Allelopathic and Bloom-Forming Picocyanobacteria in a Changing World
Received: 31 December 2017 / Revised: 17 January 2018 / Accepted: 17 January 2018 / Published: 20 January 2018
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Abstract
Picocyanobacteria are extremely important organisms in the world’s oceans and freshwater ecosystems. They play an essential role in primary production and their domination in phytoplankton biomass is common in both oligotrophic and eutrophic waters. Their role is expected to become even more relevant
[...] Read more.
Picocyanobacteria are extremely important organisms in the world’s oceans and freshwater ecosystems. They play an essential role in primary production and their domination in phytoplankton biomass is common in both oligotrophic and eutrophic waters. Their role is expected to become even more relevant with the effect of climate change. However, this group of photoautotrophic organisms still remains insufficiently recognized. Only a few works have focused in detail on the occurrence of massive blooms of picocyanobacteria, their toxicity and allelopathic activity. Filling the gap in our knowledge about the mechanisms involved in the proliferation of these organisms could provide a better understanding of aquatic environments. In this review, we gathered and described recent information about allelopathic activity of picocyanobacteria and occurrence of their massive blooms in many aquatic ecosystems. We also examined the relationships between climate change and representative picocyanobacterial genera from freshwater, brackish and marine ecosystems. This work emphasizes the importance of studying the smallest picoplanktonic fractions of cyanobacteria. Full article
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Open AccessArticle Responses of Oat Grains to Fusarium poae and F. langsethiae Infections and Mycotoxin Contaminations
Received: 5 December 2017 / Revised: 8 January 2018 / Accepted: 15 January 2018 / Published: 20 January 2018
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Abstract
Recent increases of Fusarium head blight (FHB) disease caused by infections with F. poae (FP) and F. langsethiae (FL) have been observed in oats. These pathogens are producers of nivalenol (NIV) and T-2/HT-2 toxin (T-2/HT-2), respectively, which are now considered major issues for
[...] Read more.
Recent increases of Fusarium head blight (FHB) disease caused by infections with F. poae (FP) and F. langsethiae (FL) have been observed in oats. These pathogens are producers of nivalenol (NIV) and T-2/HT-2 toxin (T-2/HT-2), respectively, which are now considered major issues for cereal food and feed safety. To date, the impact of FP and FL on oat grains has not yet been identified, and little is known about oat resistance elements against these pathogens. In the present study, the impact of FL and FP on oat grains was assessed under different environmental conditions in field experiments with artificial inoculations. The severity of FP and FL infection on grains were compared across three field sites, and the resistance against NIV and T-2/HT2 accumulation was assessed for seven oat genotypes. Grain weight, β-glucan content, and protein content were compared between infected and non-infected grains. Analyses of grain infection showed that FL was able to cause infection on the grain only in the field site with the highest relative humidity, whereas FP infected grains in all field sites. The FP infection of grains resulted in NIV contamination (between 30–500 μg/kg). The concentration of NIV in grains was not conditioned by environmental conditions. FL provoked an average contamination of grains with T-2/HT-2 (between 15–132 μg/kg). None of the genotypes was able to fully avoid toxin accumulation. The general resistance of oat grains against toxin accumulation was weak, and resistance against NIV accumulation was strongly impacted by the interaction between the genotype and the environment. Only the genotype with hull-less grains showed partial resistance to both NIV and T-2/HT-2 contamination. FP and FL infections could change the β-glucan content in grains, depending on the genotypes and environmental conditions. FP and FL did not have a significant impact on the thousand kernel weight (TKW) and protein content. Hence, resistance against toxin accumulation remains the only indicator of FHB resistance in oat. Our results highlight the need for new oat genotypes with enhanced resistance against both NIV and T-2/HT-2 to ensure food and feed safety. Full article
(This article belongs to the collection Understanding Mycotoxin Occurrence in Food and Feed Chains)
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Open AccessEditorial Announcing the 2018 Toxins Travel Awards for Post-Doctoral Fellows
Received: 18 January 2018 / Revised: 18 January 2018 / Accepted: 18 January 2018 / Published: 19 January 2018
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Abstract
This year we enjoyed a large number of very highy meritorious applications for our annual Toxins Travel Awards.[...] Full article
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Open AccessArticle Chronic Dietary Intake of Enniatin B in Broiler Chickens Has Low Impact on Intestinal Morphometry and Hepatic Histology, and Shows Limited Transfer to Liver Tissue
Received: 14 December 2017 / Revised: 9 January 2018 / Accepted: 15 January 2018 / Published: 18 January 2018
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Abstract
The Fusarium mycotoxin enniatin B (ENN B) is a so-called emerging mycotoxin frequently contaminating poultry feed. To investigate the impact of chronic ENN B exposure on animal health, broiler chickens were fed either a diet naturally contaminated with ENN B (2352 µg/kg) or
[...] Read more.
The Fusarium mycotoxin enniatin B (ENN B) is a so-called emerging mycotoxin frequently contaminating poultry feed. To investigate the impact of chronic ENN B exposure on animal health, broiler chickens were fed either a diet naturally contaminated with ENN B (2352 µg/kg) or a control diet (135 µg/kg) for 2, 7, 14, or 21 days. ENN B concentrations were determined in plasma and liver using a validated ultra-high performance liquid chromatography—tandem mass spectrometry UHPLC-MS/MS method. Liver was evaluated histologically, and the villus length and crypt depth of the duodenum, jejunum, and ileum were measured. Histopathology of the livers did not reveal major abnormalities. Feeding an ENN B-contaminated diet could possibly inhibit the proliferation of enterocytes in the duodenal crypts, but did not affect villus length, crypt depth, or villus length-crypt depth ratio of the jejunum and ileum. ENN B levels in plasma and liver were significantly higher in the ENN B-fed group and ranged between <25–264 pg/mL and <0.05–0.85 ng/g, respectively. ENN B carry-over rates from feed to liver tissue were 0.005–0.014% and 0.034–0.109% in the ENN B and control group, respectively. Carry-over rates were low and indicated a limited contribution of poultry tissue-derived products to the total dietary ENN B intake for humans. The above results support the opinion of the European Food Safety Authority stating that adverse health effects from ENN B in broiler chickens are unlikely. Full article
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Open AccessEditorial “Bacterial Toxins” Section in the Journal Toxins: A Fantastic Multidisciplinary Interplay between Bacterial Pathogenicity Mechanisms, Physiological Processes, Genomic Evolution, and Subsequent Development of Identification Methods, Efficient Treatment, and Prevention of Toxigenic Bacteria
Received: 16 January 2018 / Revised: 16 January 2018 / Accepted: 16 January 2018 / Published: 18 January 2018
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Abstract
Toxins are powerful pathogenicity factors produced by certain bacteria, fungi, animals, and plants which mediate drastic interactions of these pathogens on the organism host[...] Full article
(This article belongs to the Section Bacterial Toxins)
Open AccessFeature PaperArticle The Peptide PnPP-19, a Spider Toxin Derivative, Activates μ-Opioid Receptors and Modulates Calcium Channels
Received: 22 December 2017 / Revised: 11 January 2018 / Accepted: 12 January 2018 / Published: 15 January 2018
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Abstract
The synthetic peptide PnPP-19 comprehends 19 amino acid residues and it represents part of the primary structure of the toxin δ-CNTX-Pn1c (PnTx2-6), isolated from the venom of the spider Phoneutria nigriventer. Behavioural tests suggest that PnPP-19 induces antinociception by activation of CB1,
[...] Read more.
The synthetic peptide PnPP-19 comprehends 19 amino acid residues and it represents part of the primary structure of the toxin δ-CNTX-Pn1c (PnTx2-6), isolated from the venom of the spider Phoneutria nigriventer. Behavioural tests suggest that PnPP-19 induces antinociception by activation of CB1, μ and δ opioid receptors. Since the peripheral and central antinociception induced by PnPP-19 involves opioid activation, the aim of this work was to identify whether this synthetic peptide could directly activate opioid receptors and investigate the subtype selectivity for μ-, δ- and/or κ-opioid receptors. Furthermore, we also studied the modulation of calcium influx driven by PnPP-19 in dorsal root ganglion neurons, and analyzed whether this modulation was opioid-mediated. PnPP-19 selectively activates μ-opioid receptors inducing indirectly inhibition of calcium channels and hereby impairing calcium influx in dorsal root ganglion (DRG) neurons. Interestingly, notwithstanding the activation of opioid receptors, PnPP-19 does not induce β-arrestin2 recruitment. PnPP-19 is the first spider toxin derivative that, among opioid receptors, selectively activates μ-opioid receptors. The lack of β-arrestin2 recruitment highlights its potential for the design of new improved opioid agonists. Full article
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology) Printed Edition available
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Open AccessArticle Comparative Response of the Hepatic Transcriptomes of Domesticated and Wild Turkey to Aflatoxin B1
Received: 29 November 2017 / Revised: 8 January 2018 / Accepted: 10 January 2018 / Published: 13 January 2018
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Abstract
The food-borne mycotoxin aflatoxin B1 (AFB1) poses a significant risk to poultry, which are highly susceptible to its hepatotoxic effects. Domesticated turkeys (Meleagris gallopavo) are especially sensitive, whereas wild turkeys (M. g. silvestris) are more resistant.
[...] Read more.
The food-borne mycotoxin aflatoxin B1 (AFB1) poses a significant risk to poultry, which are highly susceptible to its hepatotoxic effects. Domesticated turkeys (Meleagris gallopavo) are especially sensitive, whereas wild turkeys (M. g. silvestris) are more resistant. AFB1 toxicity entails bioactivation by hepatic cytochrome P450s to the electrophilic exo-AFB1-8,9-epoxide (AFBO). Domesticated turkeys lack functional hepatic GST-mediated detoxification of AFBO, and this is largely responsible for the differences in resistance between turkey types. This study was designed to characterize transcriptional changes induced in turkey livers by AFB1, and to contrast the response of domesticated (susceptible) and wild (more resistant) birds. Gene expression responses to AFB1 were examined using RNA-sequencing. Statistically significant differences in gene expression were observed among treatment groups and between turkey types. Expression analysis identified 4621 genes with significant differential expression (DE) in AFB1-treated birds compared to controls. Characterization of DE transcripts revealed genes dis-regulated in response to toxic insult with significant association of Phase I and Phase II genes and others important in cellular regulation, modulation of apoptosis, and inflammatory responses. Constitutive expression of GSTA3 was significantly higher in wild birds and was significantly higher in AFB1-treated birds when compared to controls for both genetic groups. This pattern was also observed by qRT-PCR in other wild and domesticated turkey strains. Results of this study emphasize the differential response of these genetically distinct birds, and identify genes and pathways that are differentially altered in aflatoxicosis. Full article
(This article belongs to the collection Aflatoxins)
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Open AccessArticle Transketolase Is Identified as a Target of Herbicidal Substance α-Terthienyl by Proteomics
Received: 28 November 2017 / Revised: 27 December 2017 / Accepted: 11 January 2018 / Published: 12 January 2018
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Abstract
α-terthienyl is a natural phytotoxin isolated originally from Flaveria bidentis (L.) Kuntze. The bioassay presented here shows the strong herbicidal activity of α-terthienyl on Digitaria sanguinalis, Arabidopsis thaliana and Chlamydomonas reinhardtii. The α-terthienyl-induced response of A. thaliana at
[...] Read more.
α-terthienyl is a natural phytotoxin isolated originally from Flaveria bidentis (L.) Kuntze. The bioassay presented here shows the strong herbicidal activity of α-terthienyl on Digitaria sanguinalis, Arabidopsis thaliana and Chlamydomonas reinhardtii. The α-terthienyl-induced response of A. thaliana at the protein level was analyzed at different times. Changes in the protein expression profiles were analyzed by two-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry (LC-MS/MS) mass spectrometry. Sixteen protein spots were identified that showed reproducible changes in the expression of at least 2-fold when compared to the control. Among these 16 spots, three were up-regulated and 13 were down-regulated. The decreased expression of several proteins associated with energy production and carbon metabolism suggested that these processes were affected by α-terthienyl. To search for the candidate proteins in this screen, A. thaliana T-DNA mutants of the candidate proteins were used to test their susceptibility to α-terthienyl. Amongst the others, attkl1, a mutant of transketolase, exhibited a significantly lower sensitivity to α-terthienyl when hit compared with Col-0. Based on the identification of the proteins associated with the response to α-terthienyl by proteomics, a candidate target protein transketolase was identified. Full article
(This article belongs to the Section Plant Toxins)
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Open AccessArticle Molecular and Physiological Effects on the Small Intestine of Weaner Pigs Following Feeding with Deoxynivalenol-Contaminated Feed
Received: 23 November 2017 / Revised: 4 January 2018 / Accepted: 9 January 2018 / Published: 12 January 2018
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Abstract
We intended to assess how exposure of piglets to deoxynivalenol (DON)-contaminated feed impacted their growth, immune response and gut development. Piglets were fed traditional Phase I, Phase II and Phase III diets with the control group receiving 0.20–0.40 ppm DON (referred to as
[...] Read more.
We intended to assess how exposure of piglets to deoxynivalenol (DON)-contaminated feed impacted their growth, immune response and gut development. Piglets were fed traditional Phase I, Phase II and Phase III diets with the control group receiving 0.20–0.40 ppm DON (referred to as the Control group) and treatment group receiving much higher level of DON-contaminated wheat (3.30–3.80 ppm; referred to as DON-contaminated group). Feeding a DON-contaminated diet had no impact on average daily feed intake (ADFI) (p < 0.08) or average daily gain (ADG) (p > 0.10) but it did significantly reduce body weight over time relative to the control piglets (p < 0.05). Cytokine analysis after initial exposure to the DON-contaminated feed did not result in significant differences in serum interleukin (IL) IL1β, IL-8, IL-13, tumor necrosis factor (TNF)-α or interferon (IFN)-γ. After day 24, no obvious changes in jejunum or ileum gut morphology, histology or changes in gene expression for IL-1β, IL-6, IL-10, TNFα, or Toll-like receptor (TLR)-4 genes. IL-8 showed a trend towards increased expression in the ileum in DON-fed piglets. A significant increase in gene expression for claudin (CLDN) 7 gene expression and a trend towards increased CLDN 2-expression was observed in the ileum in piglets fed the highly DON-contaminated wheat. Because CLDN localization was not negatively affected, we believe that it is unlikely that gut permeability was affected. Exposure to DON-contaminated feed did not significantly impact weaner piglet performance or gut physiology. Full article
(This article belongs to the Special Issue Effects of Mycotoxins on the Intestine)
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Open AccessEditor’s ChoiceArticle Analysis of Microcystins in Cyanobacterial Blooms from Freshwater Bodies in England
Received: 29 November 2017 / Revised: 2 January 2018 / Accepted: 8 January 2018 / Published: 11 January 2018
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Abstract
Cyanobacterial blooms in freshwater bodies in England are currently monitored reactively, with samples containing more than 20,000 cells/mL of potentially toxin-producing species by light microscopy resulting in action by the water body owner. Whilst significantly reducing the risk of microcystin exposure, there is
[...] Read more.
Cyanobacterial blooms in freshwater bodies in England are currently monitored reactively, with samples containing more than 20,000 cells/mL of potentially toxin-producing species by light microscopy resulting in action by the water body owner. Whilst significantly reducing the risk of microcystin exposure, there is little data describing the levels of these toxins present in cyanobacterial blooms. This study focused on the quantitative LC-MS/MS analysis of microcystins in freshwater samples, collected across England during 2016 and found to contain potentially toxin-producing cyanobacteria. More than 50% of samples contained quantifiable concentrations of microcystins, with approximately 13% exceeding the WHO medium health threshold of 20 μg/L. Toxic samples were confirmed over a nine-month period, with a clear increase in toxins during late summer, but with no apparent geographical patterns. No statistical relationships were found between total toxin concentrations and environmental parameters. Complex toxin profiles were determined and profile clusters were unrelated to cyanobacterial species, although a dominance of MC-RR was determined in water samples from sites associated with lower rainfall. 100% of samples with toxins above the 20 μg/L limit contained cell densities above 20,000 cells/mL or cyanobacterial scum, showing the current regime is suitable for public health. Conversely, with only 18% of cell density threshold samples having total microcystins above 20 μg/L, there is the potential for reactive water closures to unnecessarily impact upon the socio-economics of the local population. In the future, routine analysis of bloom samples by LC-MS/MS would provide a beneficial confirmatory approach to the current microscopic assessment, aiding both public health and the needs of water users and industry. Full article
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Open AccessReview Updated Overview of Infrared Spectroscopy Methods for Detecting Mycotoxins on Cereals (Corn, Wheat, and Barley)
Received: 27 November 2017 / Revised: 21 December 2017 / Accepted: 3 January 2018 / Published: 10 January 2018
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Abstract
Each year, mycotoxins cause economic losses of several billion US dollars worldwide. Consequently, methods must be developed, for producers and cereal manufacturers, to detect these toxins and to comply with regulations. Chromatographic reference methods are time consuming and costly. Thus, alternative methods such
[...] Read more.
Each year, mycotoxins cause economic losses of several billion US dollars worldwide. Consequently, methods must be developed, for producers and cereal manufacturers, to detect these toxins and to comply with regulations. Chromatographic reference methods are time consuming and costly. Thus, alternative methods such as infrared spectroscopy are being increasingly developed to provide simple, rapid, and nondestructive methods to detect mycotoxins. This article reviews research conducted over the last eight years into the use of near-infrared and mid-infrared spectroscopy to monitor mycotoxins in corn, wheat, and barley. More specifically, we focus on the Fusarium species and on the main fusariotoxins of deoxynivalenol, zearalenone, and fumonisin B1 and B2. Quantification models are insufficiently precise to satisfy the legal requirements. Sorting models with cutoff levels are the most promising applications. Full article
(This article belongs to the collection Understanding Mycotoxin Occurrence in Food and Feed Chains)
Open AccessEditorial Acknowledgement to Reviewers of Toxins in 2017
Received: 9 January 2018 / Revised: 9 January 2018 / Accepted: 9 January 2018 / Published: 9 January 2018
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Abstract
Peer review is an essential part in the publication process, ensuring that Toxins maintains high quality standards for its published papers.[...] Full article
Open AccessFeature PaperEditor’s ChoiceReview Sea Anemones: Quiet Achievers in the Field of Peptide Toxins
Received: 18 December 2017 / Revised: 4 January 2018 / Accepted: 4 January 2018 / Published: 8 January 2018
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Abstract
Sea anemones have been understudied as a source of peptide and protein toxins, with relatively few examined as a source of new pharmacological tools or therapeutic leads. This is surprising given the success of some anemone peptides that have been tested, such as
[...] Read more.
Sea anemones have been understudied as a source of peptide and protein toxins, with relatively few examined as a source of new pharmacological tools or therapeutic leads. This is surprising given the success of some anemone peptides that have been tested, such as the potassium channel blocker from Stichodactyla helianthus known as ShK. An analogue of this peptide, ShK-186, which is now known as dalazatide, has successfully completed Phase 1 clinical trials and is about to enter Phase 2 trials for the treatment of autoimmune diseases. One of the impediments to the exploitation of sea anemone toxins in the pharmaceutical industry has been the difficulty associated with their high-throughput discovery and isolation. Recent developments in multiple ‘omic’ technologies, including genomics, transcriptomics and proteomics, coupled with advanced bioinformatics, have opened the way for large-scale discovery of novel sea anemone toxins from a range of species. Many of these toxins will be useful pharmacological tools and some will hopefully prove to be valuable therapeutic leads. Full article
(This article belongs to the Special Issue Selected Papers from the 2017 Venoms to Drugs Conference)
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Open AccessArticle Biological and Proteolytic Variation in the Venom of Crotalus scutulatus scutulatus from Mexico
Received: 20 November 2017 / Revised: 24 December 2017 / Accepted: 4 January 2018 / Published: 8 January 2018
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Abstract
Rattlesnake venoms may be classified according to the presence/absence and relative abundance of the neurotoxic phospholipases A2s (PLA2s), such as Mojave toxin, and snake venom metalloproteinases (SVMPs). In Mexico, studies to determine venom variation in Mojave Rattlesnakes (Crotalus
[...] Read more.
Rattlesnake venoms may be classified according to the presence/absence and relative abundance of the neurotoxic phospholipases A 2 s (PLA 2 s), such as Mojave toxin, and snake venom metalloproteinases (SVMPs). In Mexico, studies to determine venom variation in Mojave Rattlesnakes (Crotalus scutulatus scutulatus) are limited and little is known about the biological and proteolytic activities in this species. Tissue (34) and venom (29) samples were obtained from C. s. scutulatus from different locations within their distribution in Mexico. Mojave toxin detection was carried out at the genomic (by PCR) and protein (by ELISA) levels for all tissue and venom samples. Biological activity was tested on representative venoms by measuring LD 50 and hemorrhagic activity. To determine the approximate amount of SVMPs, 15 venoms were separated by RP-HPLC and variation in protein profile and proteolytic activity was evaluated by SDS-PAGE (n = 28) and Hide Powder Azure proteolytic analysis (n = 27). Three types of venom were identified in Mexico which is comparable to the intraspecific venom diversity observed in the Sonoran Desert of Arizona, USA: Venom Type A (∼Type II), with Mojave toxin, highly toxic, lacking hemorrhagic activity, and with scarce proteolytic activity; Type B (∼Type I), without Mojave toxin, less toxic than Type A, highly hemorrhagic and proteolytic; and Type A + B, containing Mojave toxin, as toxic as venom Type A, variable in hemorrhagic activity and with intermediate proteolytic activity. We also detected a positive correlation between SVMP abundance and hemorrhagic and proteolytic activities. Although more sampling is necessary, our results suggest that venoms containing Mojave toxin and venom lacking this toxin are distributed in the northwest and southeast portions of the distribution in Mexico, respectively, while an intergradation in the middle of both zones is present. Full article
(This article belongs to the Section Animal Venoms)
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Open AccessReview Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update
Received: 28 November 2017 / Revised: 21 December 2017 / Accepted: 23 December 2017 / Published: 8 January 2018
Cited by 4 | PDF Full-text (1440 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle
[...] Read more.
In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered. The inflammatory, cardio-vascular and fibrogenic systems were those most frequently affected and they are one by one major actors in the high morbidity and mortality of CKD but also the mechanisms that have most frequently been studied. A scoring system was built with the intention to classify the reviewed compounds according to the experimental evidence of their toxicity (number of systems affected) and overall experimental and clinical evidence. Among the highest globally scoring solutes were 3 small water-soluble compounds [asymmetric dimethylarginine (ADMA); trimethylamine-N-oxide (TMAO); uric acid], 6 protein bound compounds or groups of protein bound compounds [advanced glycation end products (AGEs); p-cresyl sulfate; indoxyl sulfate; indole acetic acid; the kynurenines; phenyl acetic acid;] and 3 middle molecules [β2-microglobulin; ghrelin; parathyroid hormone). In general, more experimental data were provided for the protein bound molecules but for almost half of them clinical evidence was missing in spite of robust experimental data. The picture emanating is one of a complex disorder, where multiple factors contribute to a multisystem complication profile, so that it seems of not much use to pursue a decrease of concentration of a single compound. Full article
(This article belongs to the Special Issue Novel Issues in Uremic Toxicity)
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