RESUMO
Ongoing research on cyanotoxins, driven by the socioeconomic impact of harmful algal blooms, emphasizes the critical necessity of elucidating the toxicological profiles of algal cell extracts and pure toxins. This study comprehensively compares Raphidiopsis raciborskii dissolved extract (RDE) and cylindrospermopsin (CYN) based on Daphnia magna assays. Both RDE and CYN target vital organs and disrupt reproduction, development, and digestion, thereby causing acute and chronic toxicity. Disturbances in locomotion, reduced behavioral activity, and weakened swimming capability in D. magna have also been reported for both RDE and CYN, indicating the insufficiency of conventional toxicity evaluation parameters for distinguishing between the toxic effects of algal extracts and pure cyanotoxins. Additionally, chemical profiling revealed the presence of highly active tryptophan-, humic acid-, and fulvic acid-like fluorescence compounds in the RDE, along with the active constituents of CYN, within a 15-day period, demonstrating the chemical complexity and dynamics of the RDE. Transcriptomics was used to further elucidate the distinct molecular mechanisms of RDE and CYN. They act diversely in terms of cytotoxicity, involving oxidative stress and response, protein content, and energy metabolism, and demonstrate distinct modes of action in neurofunctions. In essence, this study underscores the distinct toxicity mechanisms of RDE and CYN and emphasizes the necessity for context- and objective-specific toxicity assessments, advocating nuanced approaches to evaluate the ecological and health implications of cyanotoxins, thereby contributing to the precision of environmental risk assessments.
Assuntos
Alcaloides , Toxinas Bacterianas , Toxinas de Cianobactérias , Cianobactérias , Daphnia , Animais , Toxinas Bacterianas/toxicidade , Daphnia/efeitos dos fármacos , Alcaloides/toxicidade , Cianobactérias/química , Uracila/análogos & derivados , Uracila/toxicidade , Extratos Celulares/química , Extratos Celulares/farmacologia , Proliferação Nociva de AlgasRESUMO
The rise in cyanobacterial blooms due to eutrophication and climate change has increased cyanotoxin presence in water. Most current water treatment plants do not effectively remove these toxins, posing a potential risk to public health. This study introduces a water treatment approach using nanostructured beads containing magnetic nanoparticles (MNPs) for easy removal from liquid suspension, coated with different adsorbent materials to eliminate cyanotoxins. Thirteen particle types were produced using activated carbon, CMK-3 mesoporous carbon, graphene, chitosan, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidised cellulose nanofibers (TOCNF), esterified pectin, and calcined lignin as an adsorbent component. The particles' effectiveness for detoxification of microcystin-LR (MC-LR), cylindrospermopsin (CYN), and anatoxin-A (ATX-A) was assessed in an aqueous solution. Two particle compositions presented the best adsorption characteristics for the most common cyanotoxins. In the conditions tested, mesoporous carbon nanostructured particles, P1-CMK3, provide good removal of MC-LR and Merck-activated carbon nanostructured particles, P9-MAC, can remove ATX-A and CYN with high and fair efficacy, respectively. Additionally, in vitro toxicity of water treated with each particle type was evaluated in cultured cell lines, revealing no alteration of viability in human renal, neuronal, hepatic, and intestinal cells. Although further research is needed to fully characterise this new water treatment approach, it appears to be a safe, practical, and effective method for eliminating cyanotoxins from water.
Assuntos
Toxinas Bacterianas , Toxinas de Cianobactérias , Toxinas Marinhas , Microcistinas , Purificação da Água , Toxinas de Cianobactérias/química , Humanos , Microcistinas/toxicidade , Microcistinas/química , Microcistinas/isolamento & purificação , Toxinas Marinhas/toxicidade , Toxinas Marinhas/química , Toxinas Marinhas/isolamento & purificação , Purificação da Água/métodos , Adsorção , Toxinas Bacterianas/toxicidade , Toxinas Bacterianas/química , Toxinas Bacterianas/isolamento & purificação , Alcaloides/química , Alcaloides/toxicidade , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Tropanos/química , Tropanos/toxicidade , Tropanos/isolamento & purificação , Nanoestruturas/química , Nanoestruturas/toxicidade , Uracila/análogos & derivados , Uracila/química , Uracila/toxicidade , Cianobactérias/química , Sobrevivência Celular/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/químicaRESUMO
Cylindrospermopsin (CYN), a cyanobacterial toxin, has been detected in the global water environment. However, information concerning the potential environmental risk of CYN is limited, since the majority of previous studies have mainly focused on the adverse health effects of CYN through contaminated drinking water. The present study reported that CYN at environmentally relevant levels (0.1-100⯵g/L) can significantly enhance the conjugative transfer of RP4 plasmid in Escherichia coli genera, wherein application of 10⯵g/L of CYN led to maximum fold change of â¼6.5- fold at 16â¯h of exposure. Meanwhile, evaluation of underlying mechanisms revealed that environmental concentration of CYN exposure could increase oxidative stress in the bacterial cells, resulting in ROS overproduction. In turn, this led to an upregulation of antioxidant enzyme-related genes to avoid ROS attack. Further, inhibition of the synthesis of glutathione (GSH) was also detected, which led to the rapid depletion of GSH in cells and thus triggered the SOS response and promoted the conjugative transfer process. Increase in cell membrane permeability, upregulation of expression of genes related to pilus generation, ATP synthesis, and RP4 gene expression were also observed. These results highlight the potential impact on the spread of antimicrobial resistance in water environments.
Assuntos
Alcaloides , Toxinas Bacterianas , Toxinas de Cianobactérias , Escherichia coli , Glutationa , Plasmídeos , Uracila , Plasmídeos/genética , Glutationa/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Toxinas Bacterianas/toxicidade , Uracila/análogos & derivados , Uracila/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Conjugação Genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genéticaRESUMO
Benthic freshwater cyanobacteria have the potential to produce toxins. Compared with more extensively studied plankton species, little is known about the impact of harmful benthic cyanobacteria on aquatic organisms. As demersal fish are usually in direct contact with benthic cyanobacteria, it is important to understand their interactive effects. This study investigated the physio-chemical responses of two demersal fish (Xenocypris davidi and Crucian carp) after exposure to benthic Oscillatoria (producing cylindrospermopsin, 2 × 106 cells/mL) for 7 days. Interestingly, benthic Oscillatoria had less adverse effects on X. davidi than C. carp. The two demersal fish effectively ingested Oscillatoria, but Oscillatoria cell sheathes could not be fully digested in C. carp intestines and led to growth inhibition. Oscillatoria consumption induced oxidative stress and triggered alterations in detoxification enzyme activities in the X. davidi liver. Superoxide dismutase (SOD) and glutathione reductase (GR) activities significantly increased in the C. carp liver, but catalase (CAT) and detoxification enzymes glutathione S-transferase (GST) and glutathione (GSH) activities were insignificantly changed. This suggested that C. carp may have a relatively weak detoxification capacity for toxic Oscillatoria. Oscillatoria ingestion led to more pronounced liver pathological changes in C. carp, including swelling, deformation, and loss of cytoskeleton structure. Simultaneously, fish consumption of Oscillatoria increased extracellular cylindrospermopsin concentration. These results provide valuable insights into the ecological risks associated with benthic cyanobacteria in aquatic ecosystems.
Assuntos
Toxinas Bacterianas , Carpas , Toxinas de Cianobactérias , Fígado , Estresse Oxidativo , Animais , Fígado/patologia , Toxinas Bacterianas/toxicidade , Cianobactérias , Antioxidantes/metabolismo , Alcaloides , Oscillatoria , Uracila/análogos & derivados , Uracila/toxicidade , Superóxido Dismutase/metabolismo , Toxinas Marinhas/toxicidadeRESUMO
There is a growing concern regarding the adverse risks exposure to cylindrospermopsin (CYN) might exert on animals and humans. However, data regarding the toxicity of this cyanotoxin to neotropical fish species are scarce. Using the fish species Poecilia reticulata, the influence of CYN concentrations equal to and above the tolerable for drinking water may produce on liver was determined by assessing biomarkers of antioxidant defense mechanisms and correlated to qualitative and semiquantitative histopathological observations. Adult females were exposed to 0.0 (Control); 0.5, 1 and 1.5 µg/L pure CYN for 24 or 96 hr, in triplicate. Subsequently the livers were extracted for biochemical assays and histopathological evaluation. Catalase (CAT) activity was significantly increased only by 1.5 µg/L CYN-treatment, at both exposure times. Glutathione -S-transferase (GST) activity presented a biphasic response for both exposure times. It was markedly decreased after exposure by 0.5 µg/L CYN treatment but significantly elevated by 1.5 µg/L CYN treatment. All CYN treatments produced histopathological alterations, as evidenced by hepatocyte cords degeneration, steatosis, inflammatory infiltration, melanomacrophage centers, vessel congestion, and areas with necrosis. Further, an IORG >35 was achieved for all treatments, indicative of the presence of severe histological alterations in P. reticulata hepatic parenchyma and stroma. Taken together, data demonstrated evidence that CYN-induced hepatotoxicity in P. reticulata appears to be associated with an imbalance of antioxidant defense mechanisms accompanied by histopathological liver alterations. It is worthy to note that exposure to low environmentally-relevant CYN concentrations might constitute a significant risk to health of aquatic organisms.
Assuntos
Toxinas Bacterianas , Poecilia , Animais , Antioxidantes/metabolismo , Toxinas Bacterianas/toxicidade , Fígado/metabolismo , Oxirredução , Estresse Oxidativo , Uracila/toxicidadeRESUMO
Anatoxin-a (ATX-a) is a cyanobacterial toxin whose occurrence has been reported worldwide and has attracted increasing scientific interest due to its toxicity. Moreover, in nature, ATX-a usually appears together with other cyanotoxins, such as cylindrospermopsin (CYN), so possible interaction phenomena could happen and should be considered for risk assessment purposes. For this reason, the aim of this work was to explore the potential mutagenicity and genotoxicity of pure ATX-a and an ATX-a/CYN mixture using a battery of in vitro assays, including the bacterial reverse-mutation assay in Salmonella typhimurium (OECD 471) and the micronucleus test (MN) (OECD 487) on L5178Y Tk+/- cells. The results showed that ATX-a was not mutagenic either alone or in combination with CYN under the conditions tested. Nevertheless, genotoxic effects were observed for both ATX-a and its mixture with CYN following the in vitro MN assay. The genotoxicity exhibited by ATX-a was only observed in the absence of S9 mix, whereas in the cyanotoxin mixture the concentration-dependent genotoxicity of ATX-a/CYN in vitro was observed only in the presence of S9. Thus, the toxicity induced by cyanotoxin mixtures may vary from that produced by toxins alone, and consequently more studies are necessary in order to perform more realistic risk assessments.
Assuntos
Toxinas Bacterianas , Mutagênicos , Mutagênicos/toxicidade , Toxinas Bacterianas/toxicidade , Microcistinas/toxicidade , Dano ao DNA , Uracila/toxicidadeRESUMO
The incidence and interest of cyanobacteria are increasing nowadays because they are able to produce some toxic secondary metabolites known as cyanotoxins. Among them, the presence of cylindrospermopsin (CYN) is especially relevant, as it seems to cause damage at different levels in the organisms: the nervous system being the one most recently reported. Usually, the effects of the cyanotoxins are studied, but not those exerted by cyanobacterial biomass. The aim of the present study was to assess the cytotoxicity and oxidative stress generation of one cyanobacterial extract of R. raciborskii non-containing CYN (CYN-), and compare its effects with those exerted by a cyanobacterial extract of C. ovalisporum containing CYN (CYN+) in the human neuroblastoma SH-SY5Y cell line. Moreover, the analytical characterization of potential cyanotoxins and their metabolites that are present in both extracts of these cultures was also carried out using Ultrahigh Performance Liquid Chromatography-Mass Spectrometry, in tandem (UHPLC-MS/MS). The results show a reduction of cell viability concentration- and time-dependently after 24 and 48 h of exposure with CYN+ being five times more toxic than CYN-. Furthermore, the reactive oxygen species (ROS) increased with time (0-24 h) and CYN concentration (0-1.11 µg/mL). However, this rise was only obtained after the highest concentrations and times of exposure to CYN-, while this extract also caused a decrease in reduced glutathione (GSH) levels, which might be an indication of the compensation of the oxidative stress response. This study is the first one performed in vitro comparing the effects of CYN+ and CYN-, which highlights the importance of studying toxic features in their natural scenario.
Assuntos
Toxinas Bacterianas , Cianobactérias , Neuroblastoma , Humanos , Toxinas Bacterianas/metabolismo , Espectrometria de Massas em Tandem , Toxinas de Cianobactérias , Estresse Oxidativo , Cianobactérias/metabolismo , Linhagem Celular , Uracila/toxicidade , Uracila/metabolismoRESUMO
Cylindrospermopsin (CYN) is a cyanotoxin with an increasing occurrence, and therefore it is important to elucidate its toxicity profile. CYN has been classified as a cytotoxin, although the scientific literature has already revealed that it affects a wide range of organs and systems. However, research on its potential immunotoxicity is still limited. Thus, this study aimed to evaluate the impact of CYN on two human cell lines representative of the immune system: THP-1 (monocytes) and Jurkat (lymphocytes). CYN reduced cell viability, leading to mean effective concentrations (EC50 24 h) of 6.00 ± 1.04 µM and 5.20 ± 1.20 µM for THP-1 and Jurkat cells, respectively, and induced cell death mainly by apoptosis in both experimental models. Moreover, CYN decreased the differentiation of monocytes to macrophages after 48 h of exposure. In addition, an up-regulation of the mRNA expression of different cytokines, such as interleukin (IL) 2, IL-8, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ), was also observed mainly after 24 h exposure in both cell lines. However, only an increase in TNF-α in THP-1 supernatants was observed by ELISA. Overall, these results suggest the immunomodulatory activity of CYN in vitro. Therefore, further research is required to evaluate the impact of CYN on the human immune system.
Assuntos
Toxinas Bacterianas , Humanos , Toxinas Bacterianas/toxicidade , Monócitos , Fator de Necrose Tumoral alfa/genética , Linfócitos T , Uracila/toxicidadeRESUMO
Microcystins (MCs) and cylindrospermopsin (CYN), although classified as hepatotoxins and cytotoxins, respectively, have been shown to also induce toxic effects in many other systems and organs. Among them, their potential endocrine disruption (ED) activity has been scarcely investigated. Considering the increasing relevance of ED on humans, mammals, and aquatic organisms, this work aimed to review the state-of-the-art regarding the toxic effects of MCs and CYN at this level. It has been evidenced that MCs have been more extensively investigated than CYN. Reported results are contradictory, with the presence or absence of effects, but experimental conditions also vary to a great extent. In general, both toxins have shown ED activity mediated by very different mechanisms, such as estrogenic responses via a binding estrogen receptor (ER), pathological changes in several organs and cells (testis, ovarian cells), and a decreased gonad-somatic index. Moreover, toxic effects mediated by reactive oxygen species (ROS), changes in transcriptional responses on several endocrine axes and steroidogenesis-related genes, and changes in hormone levels have also been reported. Further research is required in a risk assessment frame because official protocols for assessment of endocrine disrupters have not been used. Moreover, the use of advanced techniques would aid in deciphering cyanotoxins dose-response relationships in relation to their ED potential.
Assuntos
Toxinas Bacterianas , Microcistinas , Humanos , Animais , Microcistinas/toxicidade , Toxinas Bacterianas/toxicidade , Toxinas Marinhas/toxicidade , Toxinas de Cianobactérias , Uracila/toxicidade , MamíferosRESUMO
Cylindrospermopsin (CYN) is a cyanotoxin whose incidence has been increasing in the last decades. Due to its capacity to exert damage at different levels of the organism, it is considered a cytotoxin. Although the main target organ is the liver, recent studies indicate that CYN has potential toxic effects on the nervous system, both in vitro and in vivo. Thus, the aim of the present work was to study the effects of this cyanotoxin on neuronal viability and synaptic integrity in murine primary cultures of neurons exposed to environmentally relevant concentrations (0-1 µg/mL CYN) for 12, 24, and 48 h. The results demonstrate a concentration- and time-dependent decrease in cell viability; no cytotoxicity was detected after exposure to the cyanotoxin for 12 h, while all of the concentrations assayed decreased this parameter after 48 h. Furthermore, CYN was also demonstrated to exert damage at the synaptic level in a murine primary neuronal culture in a concentration- and time-dependent manner. These data highlight the importance of studying the neurotoxic properties of this cyanotoxin in different experimental models.
Assuntos
Toxinas Bacterianas , Uracila , Alcaloides , Animais , Toxinas Bacterianas/toxicidade , Pareamento Cromossômico , Toxinas de Cianobactérias , Camundongos , Neurônios , Uracila/toxicidadeRESUMO
Cylindrospermopsin (CYN) is a water-soluble cyanotoxin that has been linked to several cases of poisoning in the world. In vitro studies have shown that CYN acts as an endocrine disruptor by inhibiting progesterone synthesis in primary cell cultures of women, showing estrogenic activity. However, in vivo assessment of CYN in the female and male reproductive systems remains unknown. We thus aimed to evaluate the in vivo effects of CYN in both the female and male reproductive systems of mice. A single intraperitoneal exposure to 64 µg of CYN/kg body weight was performed in females. Estrous cycle was evaluated daily by vaginal cytology, and serum progesterone and estradiol levels were measured after 50 days. We showed an impairment in the estrous cycle as well as a decrease in circulating plasma progesterone levels. In males, weekly intraperitoneal doses of 20 µg of CYN/kg body weight were given and groups were killed after one, two, or four doses. CYN increased the testosterone levels in the groups that received one or two doses of CYN. Additionally, CYN induced a transient increase in spermatozoa in males after four doses. Our results highlight that CYN interferes with both male and female reproductive systems and may lead to infertility. As far as we know, this is the first report showing the impacts of CYN on the mammalian reproductive system, suggesting a threat from this cyanotoxin to human and environmental health.
Assuntos
Toxinas Bacterianas , Disruptores Endócrinos , Alcaloides , Animais , Toxinas Bacterianas/toxicidade , Peso Corporal , Toxinas de Cianobactérias , Disruptores Endócrinos/toxicidade , Estradiol , Ciclo Estral , Feminino , Humanos , Masculino , Mamíferos , Camundongos , Progesterona , Espermatogênese , Testosterona , Uracila/toxicidade , ÁguaRESUMO
Drinking water treatment ultimately aims to provide safe and harmless drinking water. Therefore, the suitability of a treatment process should not only be assessed based on reducing the concentration os a pollutant concentration but, more importantly, on reducing its toxicity. Hence, the main objective of this study was to answer whether the degradation of a highly toxic compound of global concern for drinking water equals its detoxification. We, therefore, investigated the treatment of cylindrospermopsin (CYN) by â¢OH and SO4-⢠produced in Fenton and Fenton-like reactions. Although SO4-⢠radicals removed the toxin more effectively, both radical species substantially degraded CYN. The underlying degradation mechanisms were similar for both radical species and involved hydroxylation, dehydrogenation, decarboxylation, sulfate group removal, ring cleavage, and further fragmentation. The hydroxymethyl uracil and tricyclic guanidine moieties were the primary targets. Furthermore, the residual toxicity, assessed by a 3-dimensional human in vitro liver model, was substantially reduced during the treatment by both radical species. Although the results indicated that some of the formed degradation products might still be toxic, the overall reduction of the toxicity together with the proposed degradation pathways allowed us to conclude: "Yes, degradation of CYN equals its detoxification!".
Assuntos
Toxinas Bacterianas , Poluentes Químicos da Água , Alcaloides , Toxinas de Cianobactérias , Humanos , Oxirredução , Sulfatos , Uracila/toxicidade , Poluentes Químicos da Água/toxicidadeRESUMO
Impact of macrophyte Lemna trisulca on the growth rate and synthesis of cylindrospermopsin (CYN) by cyanobacterium Raphidiopsis raciborskii was determined. The presence of L. trisulca inhibited the biomass accumulation of the cyanobacterium by 25% compared to the control during co-cultivation. The simultaneous cultivation of these organisms slightly affected the inhibition of macrophyte growth rate by 5.5% compared to the control. However, no morphological changes of L. trisulca after incubation with cyanobacteria were observed. It was also shown that the long-term (35 days) co-cultivation of R. raciborskii and L. trisulca led to a decrease in CYN concentration in media and cyanobacterial cells by 32 and 38%, respectively, compared to the values obtained for independent cultivation of cyanobacterium. Excessive absorption of phosphate ions by L. trisulca from the medium compared to nitrate ions led to a significant increase in the nitrate:phosphate ratio in the media, which inhibits the development of cyanobacterium. The obtained results indicate that L. trisulca in the natural environment may affect the physiology of cyanobacteria. The presented study is the first assessment of the allelopathic interaction of macrophyte and R. raciborskii.
Assuntos
Alcaloides , Araceae , Cylindrospermopsis , Toxinas de Cianobactérias , Uracila/toxicidadeRESUMO
The cyanotoxin cylindrospermopsin (CYN) is the second biggest cause of poisoning worldwide, both in humans and animals. Although CYN primarily affects the aquatic environments and can be absorbed in fishes by multiple routes, data reporting its toxicity and mechanism of action are still scarce in this group. Using P. reticulata as model species, it was evaluated whether CYN promotes mutagenic and genotoxic effects in different fish target tissues. Adult females were exposed in a static way to 0 (control), 0.5, 1.0, and 1.5 µg L-1 of pure CYN for 24 and 96 hours. For the first time, DNA damage was detected in fish brain after CYN exposition. In brain cells, a concentration-response DNA damage was observed for both exposure times, suggesting a direct or indirect action of CYN in neurotoxicity. For the liver cells, 96 hours caused an increase in DNA damage, as well the highest percentage of DNA in the tail was reached when used 1.5 µg L-1 of CYN. In peripheral blood cells, an increase in DNA damage was observed for all tested concentrations after 96 hours. In erythrocytes, micronuclei frequency was higher at 1.5 µg L-1 treatment while the erythrocyte nuclear abnormalities (ENA) frequency was significantly higher even at the lowest CYN concentration. Such data demonstrated that acute exposition to CYN promotes genotoxicity in the brain, liver, and blood cells of P. reticulata, as well mutagenicity in erythrocytes. It rises an alert regarding to the toxic effects of CYN for aquatic organisms as well as for human health.
Assuntos
Alcaloides , Poecilia , Adulto , Animais , Toxinas de Cianobactérias , Dano ao DNA , Feminino , Humanos , Uracila/toxicidadeRESUMO
The cyanotoxin cylindrospermopsin (CYN), a toxic metabolite from cyanobacteria, is of particular concern due to its cosmopolitan occurrence, aquatic bioaccumulation, and multi-organ toxicity. CYN is the second most often recorded cyanotoxin worldwide, and cases of human morbidity and animal mortality are associated with ingestion of CYN contaminated water. The toxin poses a great challenge for drinking water treatment plants and public health authorities. CYN, with the major toxicity manifested in the liver, is cytotoxic, genotoxic, immunotoxic, neurotoxic and may be carcinogenic. Adverse effects are also reported for endocrine and developmental processes. We present a comprehensive review of CYN over the past four decades since its first reported poisoning event, highlighting its global occurrence, biosynthesis, toxicology, removal, and monitoring. In addition, current data gaps are identified, and future directions for CYN research are outlined. This review is beneficial for understanding the ins and outs of this environmental pollutant, and for robustly assessing health hazards posed by CYN exposure to humans and other organisms.
Assuntos
Alcaloides , Toxinas Bacterianas , Cianobactérias , Animais , Toxinas de Cianobactérias , Humanos , Uracila/toxicidadeRESUMO
Raphidiopsis (Cylindrospermopsis) raciborskii, a globally distributed bloom-forming cyanobacterium, produces either the cytotoxin cylindrospermopsin (CYL) in Oceania, Asia and Europe or the neurotoxin saxitoxin (STX) and analogues (paralytic shellfish poison, PSP) in South America (encoded by sxt genetic cluster) and none of them in Africa. Nevertheless, this particular geographic pattern is usually overlooked in current hypotheses about the species dispersal routes. Here, we combined genomics, phylogenetic analyses, toxicity data and a literature survey to unveil the evolutionary history and spread of the species. Phylogenies based on 354 orthologous genes from all the available genomes and ribosomal ITS sequences of the taxon showed two well-defined clades: the American, having the PSP producers; and the Oceania/Europe/Asia, including the CYL producers. We propose central Africa as the original dispersion center (non-toxic populations), reaching North Africa and North America (in former Laurasia continent). The ability to produce CYL probably took place in populations that advanced to sub-Saharan Africa and then to Oceania and South America. According to the genomic context of the sxt cluster found in PSP-producer strains, this trait was acquired once by horizontal transfer in South America, where the ability to produce CYL was lost.
Assuntos
Toxinas Bacterianas/toxicidade , Cylindrospermopsis/classificação , Cylindrospermopsis/genética , Genômica , Filogenia , Filogeografia , Saxitoxina/toxicidade , Uracila/análogos & derivados , Alcaloides , Sequência Conservada/genética , Toxinas de Cianobactérias , Funções Verossimilhança , Família Multigênica , Sintenia/genética , Uracila/toxicidadeRESUMO
The propensity of 5-formyluracil and 5-formylcytosine, i.e. oxidative lesions and epigenetic intermediates, in acting as intrinsic DNA photosensitizers is unraveled by using a combination of molecular modeling, simulation and spectroscopy. Exploration of potential energy surfaces and non-adiabatic dynamics confirm a higher intersystem crossing rate for 5-formyluracil, whereas the kinetic models evidence different equilibria in the excited states for both compounds.
Assuntos
DNA/genética , DNA/efeitos da radiação , Epigênese Genética/genética , Simulação por Computador , Citosina/análogos & derivados , Citosina/toxicidade , DNA/química , Humanos , Cinética , Luz , Modelos Moleculares , Mutagênicos/toxicidade , Oxirredução , Uracila/análogos & derivados , Uracila/toxicidadeRESUMO
Cylindrospermopsin (CYN) is a widely distributed cyanobacterial toxin in water bodies and is considered to pose growing threats to human and environmental health. Although its potential toxicity has been reported, its effects on the vascular system are poorly understood. In this study, we examined the toxic effects of CYN on vascular development and the possible mechanism of vascular toxicity induced by CYN using zebrafish embryos and human umbilical vein endothelial cells (HUVECs). CYN exposure induced abnormal vascular development and led to an increase in the growth of common cardinal vein (CCV), in which CCV remodeling was delayed as reflected by the larger CCV area and wider ventral diameter. CYN decreased HUVECs viability, inhibited HUVECs migration, promoted HUVECs apoptosis, destroyed cytoskeleton, and increased intracellular ROS levels. Additionally, CYN could promote the expression of Bax, Bcl-2, and MLC-1 and inhibit the expression of ITGB1, Rho, ROCK, and VIM-1. Taken together, CYN may induce cytoskeleton damage and promote vascular endothelial cell apoptosis by the Rho/ROCK signaling pathway, leading to abnormal vascular development. The current results provide potential insight into the mechanism of CYN toxicity in angiocardiopathy and are beneficial for understanding the environmental risks of CYN for aquatic organisms and human health.
Assuntos
Apoptose , Toxinas Bacterianas , Uracila/análogos & derivados , Alcaloides , Animais , Apoptose/efeitos dos fármacos , Toxinas Bacterianas/toxicidade , Toxinas de Cianobactérias , Citoesqueleto/efeitos dos fármacos , Humanos , Transdução de Sinais , Cordão Umbilical/citologia , Uracila/toxicidadeRESUMO
Cylindrospermopsin (CYN) is a cyanotoxicant which occurrence is increasing due to climate change. Cylindrospermopsin is able to exert damage in the organism at several levels, among them, in the nervous system. Moreover, it is important to take into account that it is not usually present isolated in nature, but in combination with some other pollutants, being the case of the pesticide chlorpyrifos (CPF). Thus, the aim of the present work was to assess the effects of the interaction of CYN in combination with CPF in the human neuroblastoma cell line SH-SY5Y by evaluating cytotoxicity and mechanistic endpoints. The mixtures 0.25 + 21, 0.5 + 42, 1 + 84 µg/mL of CYN + CPF based on cytotoxicity results, were evaluated, and the isobologram method detected an antagonistic effect after 24 and 48 h of exposure. Moreover, although no alterations of reactive oxygen species were detected, a significant decrease of glutathione levels was observed after exposure to both, CPF alone and the combination, at all the concentrations and times of exposure assayed. In addition, CYN + CPF caused a marked decrease in the acetylcholinesterase activity, providing similar values to CPF alone. However, these effects were less severe than expected. All these findings, together with the morphological study results, point out that it is important to take into account the interaction of CYN with other pollutants. Further research is required to contribute to the risk assessment of CYN and other contaminants considering more realistic exposure scenarios.
Assuntos
Toxinas Bacterianas/toxicidade , Clorpirifos/toxicidade , Inibidores da Colinesterase/toxicidade , Poluentes Ambientais/toxicidade , Inseticidas/toxicidade , Uracila/análogos & derivados , Alcaloides , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Toxinas de Cianobactérias , Glutationa/metabolismo , Humanos , Uracila/toxicidadeRESUMO
Eutrophication of freshwater bodies increases the occurrence of toxic cyanobacterial blooms. The cyanobacterial toxin cylindrospermopsin (CYN) is receiving great interest due to its increasing presence in waterbodies. However, the toxic effects of CYN on zebrafish development are poorly understood, especially the toxicological mechanism, which is still unclear. In this study, we examined the adverse effects of CYN on embryonic development in zebrafish. CYN (2-2000â¯nM) exposure decreased embryos survival rate, hatching rate, body length and eye size in a concentration-dependent manner and caused abnormalities in embryo morphology, including pericardial edema, spinal curvature, tail deformity, uninflated swim bladder, cardiac and vascular defects. CYN at concentrations of 20â¯nM or higher significantly increased ROS level and promoted cell apoptosis in zebrafish embryos. To preliminarily elucidate the potential mechanism of zebrafish developmental toxicity caused by CYN, we examined the expression of oxidative stress- and apoptotic-related genes. CYN could promote the expression of oxidative stress-related genes (SOD1, CAT and GPx1) and induce changes in transcriptional levels of apoptotic-related genes (p53, Bax and Bcl-2). Taken together, CYN induced adverse effects on zebrafish embryos development, which may associate with oxidative stress and apoptosis. These outcomes will advance our understanding of CYN toxicity, environmental problems and health hazards caused by climate changes and eutrophication.