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1.
Environ Pollut ; 292(Pt A): 118305, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34626715

RESUMO

Due to the large-scale outbreak of Corona Virus Disease (2019), amounts of disinfecting agents was regularly used in public environments and their potential toxicity towards organisms needed to be appreciated. Thus, one mostly used cationic disinfectant, benzalkonium chlorides (BAC(C12)), was selected to assess its potential toxicity one common cyanobacteria Microcystis aeruginosa (M. aeruginosa) in this study. The aims were to explore the toxic effect and mechanism of BAC (C12) on M. aeruginosa growth within 96 h via morphological, physiological, and the relative and absolute quantification (iTRAQ)-based quantitative proteomics variations. The results found that BAC(C12) significantly inhibited cell density of M. aeruginosa at concentrations from 1 mg/L to 10 mg/L, and the 96-h EC50 value was identified to be 3.61 mg/L. Under EC50 concentration, BAC(C12) depressed the photosynthesis activities of M. aeruginosa exhibited by 36% decline of the maximum quantum yield for primary photochemistry (Fv/Fm) value and denaturation of photosynthetic organelle, caused oxidative stress response displayed by the increase of three indexes including superoxide dismutase (SOD), malondialdehyde (MDA), and the intracellular reactive oxygen species (ROS), and destroyed the integrity of cell membranes demonstrated by TEM images and the increase of ex-cellular substances. Then, the iTRAQ-based proteomic analysis demonstrated that BAC(C12) depressed photosynthesis activities through inhibiting the expressions of photosynthetic protein and photosynthetic electron transport related proteins. The suppression of electron transport also led to the increase of superoxide radicals and then posed oxidative stress on cell. Meantime, the 63.63% ascent of extracellular microcystin production of M. aeruginosa was observed, attributing to the high expression of microcystin synthesis proteins and the damage of cell membrane. In sum, BAC(C12) exposure inhibited the growth of M. aeruginosa mainly by depressing photosynthesis, inducing oxidative stress, and breaking the cell membrane. And, it enhanced the release of microcystin from the cyanobacterial cells via up-regulating the microcystin synthesis proteins and inducing the membrane damage, which could enlarge its toxicity to aquatic species.


Assuntos
Microcystis , Compostos de Benzalcônio , Cloretos , Microcistinas/metabolismo , Microcistinas/toxicidade , Microcystis/metabolismo , Fotossíntese , Proteômica
2.
Chemosphere ; 287(Pt 1): 132028, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34474382

RESUMO

Cyanotoxins including microcystins are increasing globally, escalating health risks to humans and wildlife. Freshwater fish can accumulate and retain microcystins in tissues; however, uptake and depuration studies thus far have not exposed fish to microcystins in its intracellular state (i.e., cell-bound or conserved within cyanobacteria), which is a primary route of exposure in the field, nor have they investigated sublethal molecular-level effects in tissues, limiting our knowledge of proteins responsible for microcystin toxicity pathways in pre-to-postsenescent stages of a harmful algal bloom. We address these gaps with a 2-wk study (1 wk of 'uptake' exposure to intracellular microcystins (0-40 µg L-1) produced by Microcystis aeruginosa followed by 1 wk of 'depuration' in clean water) using Rainbow Trout (Oncorhynchus mykiss) and Lake Trout (Salvelinus namaycush). Liver and muscle samples were collected throughout uptake and depuration phases for targeted microcystin quantification and nontargeted proteomics. For both species, microcystins accumulated at a higher concentration in the liver than muscle, and activated cellular responses related to oxidative stress, apoptosis, DNA repair, and carcinogenicity. However, intraspecific proteomic effects between Rainbow Trout and Lake Trout differed, and interspecific accumulation and retention of microcystins in tissues within each species also differed. We demonstrate that fish do not respond the same to cyanobacterial toxicity within and among species despite being reared in the same environment and diet.


Assuntos
Microcistinas , Microcystis , Animais , Proliferação Nociva de Algas , Humanos , Microcistinas/toxicidade , Proteômica
3.
Toxicon ; 204: 64-71, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34742780

RESUMO

In silico methodologies can be used in the discovery of new drugs for measuring toxicity, predicting effects of substances not yet analyzed by in vivo methodologies. The ADMET Predictor® software (absorption, distribution, metabolism, elimination, and toxicity [ADMET]) was used in this work to predict toxic effects of microcystin variants MC-LR, MC-YR, MC-RR, and MC-HarHar. In the case of rodents, predictive results for all analyzed variants indicated carcinogenic potential. The predictive model of respiratory sensitivity in this group differentiated microcystins into 2 categories: sensitizer (MC-LR and -YR) and non-sensitizer (MC-HarHar and -RR). Predictive results for humans indicated that MC-LR and -RR are phospholipidosis inducers; on the other hand, MC-LR showed the highest predictive value of permeability in rabbit cornea and probability of crossing lipoprotein barriers (MC-LR>-YR>-HarHar>-RR). Considering bioavailable fractions, microcystins are more likely to cause biological effects in rats than humans, showing significant differences between models. The results of ADMET predictions add valuable information on microcystin toxicity, especially in the case of variants not yet studied experimentally.


Assuntos
Cianobactérias , Microcistinas , Animais , Carcinógenos , Simulação por Computador , Microcistinas/toxicidade , Coelhos , Ratos
4.
Rev Environ Contam Toxicol ; 258: 109-150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34622370

RESUMO

Harmful cyanobacterial blooms are increasing and becoming a worldwide concern as many bloom-forming cyanobacterial species can produce toxic metabolites named cyanotoxins. These include microcystins, saxitoxins, anatoxins, nodularins, and cylindrospermopsins, which can adversely affect humans, animals, and the environment. Different methods to assess these classes of compounds in vitro and in vivo include biological, biochemical, molecular, and physicochemical techniques. Furthermore, toxic effects not attributable to known cyanotoxins can be observed when assessing bloom material. In order to determine exposures to cyanotoxins and to monitor compliance with drinking and bathing water guidelines, it is necessary to have reliable and effective methods for the analysis of these compounds. Many relatively simple low-cost methods can be employed to rapidly evaluate the potential hazard. The main objective of this mini-review is to describe the assessment of toxic cyanobacterial samples using in vitro and in vivo bioassays. Newly emerging cyanotoxins, the toxicity of analogs, or the interaction of cyanobacteria and cyanotoxins with other toxicants, among others, still requires bioassay assessment. This review focuses on some biological and biochemical assays (MTT assay, Immunohistochemistry, Micronucleus Assay, Artemia salina assay, Daphnia magna test, Radionuclide recovery, Neutral red cytotoxicity and Comet assay, Enzyme-Linked Immunosorbent Assay (ELISA), Annexin V-FITC assay and Protein Phosphatase Inhibition Assay (PPIA)) for the detection and measurement of cyanotoxins including microcystins, cylindrospermopsins, anatoxin-a, saxitoxins, and nodularins. Although most bioassay analyses often confirm the presence of cyanotoxins at low concentrations, such bioassays can be used to determine whether some strains or blooms of cyanobacteria may produce other, as yet unknown toxic metabolites. This review also aims to identify research needs and data gaps concerning the toxicity assessment of cyanobacteria.


Assuntos
Cianobactérias , Microcistinas , Animais , Humanos , Microcistinas/toxicidade , Saxitoxina , Uracila
5.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34576099

RESUMO

We were the first to previously report that microcystin-LR (MC-LR) has limited effects within the colons of healthy mice but has toxic effects within colons of mice with pre-existing inflammatory bowel disease. In the current investigation, we aimed to elucidate the mechanism by which MC-LR exacerbates colitis and to identify effective therapeutic targets. Through our current investigation, we report that there is a significantly greater recruitment of macrophages into colonic tissue with pre-existing colitis in the presence of MC-LR than in the absence of MC-LR. This is seen quantitatively through IHC staining and the enumeration of F4/80-positive macrophages and through gene expression analysis for Cd68, Cd11b, and Cd163. Exposure of isolated macrophages to MC-LR was found to directly upregulate macrophage activation markers Tnf and Il1b. Through a high-throughput, unbiased kinase activity profiling strategy, MC-LR-induced phosphorylation events were compared with potential inhibitors, and doramapimod was found to effectively prevent MC-LR-induced inflammatory responses in macrophages.


Assuntos
Inflamação/patologia , Macrófagos/patologia , Toxinas Marinhas/toxicidade , Microcistinas/toxicidade , Animais , Biomarcadores/metabolismo , Colite/genética , Colite/patologia , Colo/efeitos dos fármacos , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Naftalenos/farmacologia , Proteínas Quinases/metabolismo , Proteoma/metabolismo , Pirazóis/farmacologia , Ratos
6.
Aquat Toxicol ; 240: 105971, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34560410

RESUMO

The phenomenon of eutrophication leads to the global occurrence of algal blooms. Cyanotoxins as produced by many cyanobacterial species can lead to detrimental effects to the biome due to their stability and potential biomagnification along food webs. Therefore, understanding of the potential risks these toxins pose to the most susceptible organisms is an important prerequisite for ecological risks assessment of cyanobacteria blooms. Fishes are an important component of aquatic ecosystems that are prone to direct exposure to cyanotoxins. However, relatively few investigations have focused on measuring the toxic potentials of cyanotoxins in teleost fishes. This review comprehensively describes the major toxicological impacts (such as hepatotoxicity, neurotoxicity, immune toxicity, reproductive toxicity and cytogenotoxicity) of commonly occurring cyanotoxins in teleost fishes. The present work encompasses recent research progresses with special emphasis on the basic molecular mechanisms by which different cyanotoxins impose their toxicities in teleost fishes. The major research areas, which need to be focused on in future scientific investigations, have also been highlighted. Protein kinase inhibition, transcriptional dysregulation, disruption of redox homeostasis and the induction of apoptotic pathways appear to be the key drivers of the toxicological effects of cyanotoxins in fish. Analyses also showed that the impacts of cyanotoxins on specific reproductive processes are relatively less described in teleosts in comparison to mammalian systems. In fact, as compared to other toxicological effects of cyanotoxins, their reproductive toxicity (such as impacts on oocyte development, maturation and their hormonal regulation) is poorly understood in fish, and thus requires further studies. Furthermore, additonal studies characterizing the molecular mechanisms responsible for the cellular uptake of cyanotoxins need to be investigated.


Assuntos
Cianobactérias , Poluentes Químicos da Água , Animais , Ecossistema , Eutrofização , Peixes , Microcistinas/toxicidade , Poluentes Químicos da Água/toxicidade
7.
Ecotoxicol Environ Saf ; 223: 112610, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34365207

RESUMO

Previous studies provide comprehensive evidence of the environmental hazards and intestinal toxicity of microcystin-LR (MC-LR) exposure. However, little is known about the mechanisms underlying the injury of intestine exposed to MC-LR. Juvenile common carp (Cyprinus carpio) were exposed to MC-LR (0 and 10 µg/L) for 15 days. The results suggest that organic anion-transporting polypeptides 3a1, 4a1, 2b1, and 1d1 mediate MC-LR entry into intestinal tissues. Lesion morphological features (vacuolization, deformation and dilation of the endoplasmic reticulum [ER], absence of mitochondrial cristae in mid-intestine), up-regulated mRNA expressions of ER stress (eukaryotic translation initiation factor 2-alpha kinase 3, endoplasmic reticulum to nucleus signaling 1, activating transcription factor [ATF] 6, ATF4, DNA damage-inducible transcript 3), iron accumulation, and down-regulated activity of glutathione peroxidase (GPx) and glutathione (GSH) content were all typical characteristics of ferroptosis in intestinal tissue following MC-LR exposure. GSH levels in intestinal tissue corroborated as the most influential GSH/GPx 4- related metabolic pathway in response to MC-LR exposure. Verrucomicrobiota, Planctomycetes, Bdellovibrionota, Firmicutes and Cyanobacteria were correlated with the ferroptosis-related GSH following MC-LR exposure. These findings provide new perspectives of the ferroptosis mechanism of MC-LR-induced intestinal injury in the common carp.


Assuntos
Carpas , Ferroptose , Animais , Intestinos , Fígado , Toxinas Marinhas , Microcistinas/toxicidade
8.
Environ Pollut ; 286: 117685, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438504

RESUMO

Microcystin-LR (MC-LR) and glyphosate (GLY) have been classified as a Group 2B and Group 2A carcinogens for humans, respectively, and frequently found in aquatic ecosystems. However, data on the potential hazard of MC-LR and GLY exposure to the fish gut are relatively scarce. In the current study, a subacute toxicity test of zebrafish exposed to MC-LR (35 µg L-1) and GLY (3.5 mg L-1), either alone or in combination was performed for 21 d. The results showed that MC-LR or/and GLY treatment reduced the mRNA levels of tight junction genes (claudin-5, occludin, and zonula occludens-1) and altered the levels of diamine oxidase and D-lactic, indicating increased intestinal permeability in zebrafish. Furthermore, MC-LR and/or GLY treatment remarkably increased the levels of intestinal IL-1ß and IL-8 but decreased the levels of IL-10 and TGF-ß, indicating that MC-LR and/or GLY exposure induced an inflammatory response in the fish gut. MC-LR and/or GLY exposure also activated superoxide dismutase and catalase, generally upregulated the levels of p53, bax, bcl-2, caspase-3, and caspase-9, downregulated the levels of caspase-8 and caused notable histological injury in the fish gut. Moreover, MC-LR and/or GLY exposure also significantly altered the microbial community in the zebrafish gut and the expression of miRNAs (miR-146a, miR-155, miR-16, miR-21, and miR-223). Chronic exposure to MC-LR and/or GLY can induce intestinal damage in zebrafish, and this study is the first to demonstrate an altered gut microbiome and miRNAs in the zebrafish gut after MC-LR and GLY exposure.


Assuntos
Microbioma Gastrointestinal , MicroRNAs , Microbiota , Poluentes Químicos da Água , Animais , Glicina/análogos & derivados , Humanos , Intestinos , Toxinas Marinhas , Microcistinas/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
9.
Environ Pollut ; 287: 117644, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34426391

RESUMO

Water eutrophication caused by harmful algal blooms (HABs) occurs worldwide. It causes huge economic losses and has serious and potentially life-threatening effects on human health. In this study, the bacterium Raoultella sp. S1 with high algicidal efficiency against the harmful algae Microcystis aeruginosa was isolated from eutrophic water. The results showed that Raoultella sp. S1 initially flocculated the algae, causing the cells to sediment within 180 min and then secreted soluble algicidal substances that killed the algal cells completely within 72 h. The algicidal activity was stable across the temperature range -85.0 to 85.0 °C and across the pH range 3.00-11.00. Scanning electron microscopy (SEM) revealed the crumpling and fragmentation of cells algal cells during the flocculation and lysis stages. The antioxidant system was activated under conditions of oxidative stress, causing the increased antioxidant enzymes activities. Meanwhile, the oxidative stress response triggered by the algicidal substances markedly increased the malondialdehyde (MDA) and glutathione (GSH) content. We investigated the content of Chl-a and the relative expression levels of genes related to photosynthesis, verifying that the algicidal compounds attack the photosynthetic system by degrading the photosynthetic pigment and inhibiting the expression of key genes. Also, the results of photosynthetic efficiency and relative electric transport rate confirmed that the photosynthetic system in algal cells was severely damaged within 24 h. The algicidal effect of Raoultella sp. S1 against Microcystis aeruginosa was evaluated by analyzing the physiological response and photosynthetic system impairment of the algal cells. The concentration of microcystin-LR (MC-LR) slightly increased during the process of algal cells ruptured, and then decreased below its initial level due to the biodegradation of Raoultella sp. S1. To further investigate the algicidal mechanism of Raoultella sp. S1, the main components in the cell-free supernatant was analyzed by UHPLC-TOF-MS. Several low-molecular-weight organic acids might be responsible for the algicidal activity of Raoultella sp. S1. It is concluded that Raoultella sp. S1 has the potential to control Microcystis aeruginosa blooms.


Assuntos
Microcystis , Antioxidantes , Enterobacteriaceae , Proliferação Nociva de Algas , Humanos , Microcistinas/toxicidade , Fotossíntese
10.
Toxicology ; 460: 152887, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34352349

RESUMO

Microcystin-leucine-arginine (MLCR) is a cyanobacterial toxin, and has been demonstrated to cause neurotoxicity. In addition, MCLR has been identified as an inhibitor of protein phosphatase (PP)1 and PP2A, which are known to regulate the phosphorylation of various molecules related to synaptic excitability. Thus, in the present study, we examined whether MCLR exposure affects seizures induced by a low dose of kainic acid (KA; 0.05 µg, i.c.v.) administration. KA-induced seizure occurrence and seizure score significantly increased after repeated exposure to MCLR (2.5 or 5.0 µg/kg, i.p., once a day for 10 days), but not after acute MCLR exposure (2.5 or 5.0 µg/kg, i.p., 2 h and 30 min prior to KA administration), and hippocampal neuronal loss was consistently facilitated by repeated exposure to MCLR. In addition, repeated MCLR significantly elevated the membrane expression of kainate receptor GluK2 subunits, p-pan-protein kinase C (PKC), and p-extracellular signal-related kinase (ERK) at 1 h after KA. However, KA-induced membrane expression of Ca2+/calmodulin-dependent kinase II (CaMKII) was significantly reduced by repeated MCLR exposure. Consistent with the enhanced seizures and neurodegeneration, MCLR exposure significantly potentiated KA-induced oxidative stress and microglial activation, which was accompanied by increased expression of p-ERK and p-PKCδ in the hippocampus. The combined results suggest that repeated MCLR exposure potentiates KA-induced excitotoxicity in the hippocampus by increasing membrane GluK2 expression and enhancing oxidative stress and neuroinflammation through the modulation of p-CaMKII, p-PKC, and p-ERK.


Assuntos
Arginina/toxicidade , Ácido Caínico/toxicidade , Leucina/toxicidade , Microcistinas/toxicidade , Neurotoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Toxinas Bacterianas/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ácido Caínico/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neurotoxinas/administração & dosagem , Estresse Oxidativo/fisiologia , Convulsões/induzido quimicamente , Convulsões/metabolismo
11.
Environ Monit Assess ; 193(9): 554, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34357469

RESUMO

Cyanobacteria are important members of lake plankton, but they have the ability to form blooms and produce cyanotoxins and thus cause a number of adverse effects. Freshwater ecosystems around the world have been investigated for the distribution of cyanobacteria and their toxins and the effects they have on the ecosystems. Similar research was performed on the Fehérvárcsurgó reservoir in Hungary during 2018. Cyanobacteria were present and blooming, and the highest abundance was recorded in July (2,822,000 cells/mL). The species present were Aphanizomenon flos-aquae, Microcystis flos-aquae, Microcystis wesenbergii, Cuspidothrix issatschenkoi, Dolichospermum flos-aquae, and Snowella litoralis. In July and September, the microcystin encoding gene mcyE and the saxitoxin encoding gene sxtG were amplified in the biomass samples. While a low concentration of microcystin-RR was found in one water sample from July, analyses of Abramis brama and Carassius gibelio caught from the reservoir did not show the presence of the investigated microcystins in the fish tissue. However, several histopathological changes, predominantly in gills and kidneys, were observed in the fish, and the damage was more severe during May and especially July, which coincides with the increase in cyanobacterial biomass during the summer months. Cyanobacteria may thus have adverse effects in this ecosystem.


Assuntos
Cianobactérias , Microcystis , Animais , Aphanizomenon , Ecossistema , Monitoramento Ambiental , Hungria , Lagos , Microcistinas/análise , Microcistinas/toxicidade
12.
Toxicon ; 201: 169-176, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34450178

RESUMO

Microcystin -leucine-arginine (MC-LR), produced by freshwater cyanobacteria, is a potential pancreatic ß-cell toxin. In this study, the function of the mouse pancreatic ß-cell line, MIN6, was evaluated after MC-LR exposure, and the underlying molecular mechanisms were explored. Exposure to MC-LR for 24 h was found to inhibit cell viability and impair insulin secretion. Such findings indicate that ß-cell function would be impaired following MC-LR treatment. The microarray results revealed altered miRNA and mRNA expression profiles that might be responsible for the abnormal function of MIN6 cells. Further, miRNA-gene network analysis demonstrated that miR-29b-3p, miR-6967-5p, miR-3473, miR-7061-5p, Xkr4, Tmem178b, Scp2, Ypel2, and Kcnj11 are key miRNAs and genes in the MC-LR-induced MIN6-cell toxicity. The altered expression levels of several miRNAs (e.g., miR-320-5p, miR-770-5p, miR-99a-3p, and miR-375-5p) and genes (e.g., Pklr and Gpd2) involved in insulin secretion or the onset of diabetes were also identified in MIN6 cells after treatment with MC-LR. Collectively, these findings provide evidence of the toxic effects of MC-LR on ß-cells and the underlying molecular mechanisms of its glycometabolism toxicity. MCs may thus possibly play an important role in the development of diabetes mellitus in humans.


Assuntos
MicroRNAs , Microcistinas , Animais , Arginina , Secreção de Insulina , Leucina/toxicidade , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Microcistinas/toxicidade , RNA Mensageiro
13.
Environ Toxicol ; 36(12): 2414-2425, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34432352

RESUMO

Microcystin-leucine-arginine (MC-LR) is a toxin secreted by freshwater cyanobacteria that is considered a potential environmental risk factor for Alzheimer's disease (AD). A previous study indicated that tau protein hyperphosphorylation via protein phosphatase 2A (PP2A) and GSK-3ß inhibition was the mechanism by which MC-LR induces neurotoxicity; however, how MC-LR-induced neurotoxicity can be effectively prevented remains unclear. In this study, the reversal effect of metformin on MC-LR-induced neurotoxicity was investigated. The results showed that metformin effectively prevented tau hyperphosphorylation at Ser202 caused by MC-LR through PP2A and GSK-3b activity. The effect of metformin on PP2A activity was dependent on the inhibition of mTOR in MC-LR-treated SH-SY5Y cells. Metformin prevented spatial memory deficits in rats caused by intrahippocampal MC-LR administration. In sum, the results suggested that metformin can ameliorate the MC-LR-induced AD-like phenotype by preventing tau phosphorylation at Ser202, which was mainly mediated by mTOR-dependent PP2A and GSK-3ß activation.


Assuntos
Metformina , Proteínas tau , Animais , Glicogênio Sintase Quinase 3 beta , Toxinas Marinhas , Metformina/farmacologia , Microcistinas/toxicidade , Fosforilação , Proteína Fosfatase 2/metabolismo , Ratos , Serina-Treonina Quinases TOR , Proteínas tau/metabolismo
14.
Environ Sci Technol ; 55(15): 10422-10431, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34264629

RESUMO

The global expansion of toxic Microcystis blooms, and production of cyanotoxins including microcystins, are an increasing risk to freshwater fish. Differentiating intracellular and extracellular microcystin toxicity pathways (i.e., within and outside of cyanobacterial cells) in fish is necessary to assess the severity of risks to populations that encounter harmful algal blooms in pre-to-postsenescent stages. To address this, adult and juvenile Rainbow Trout (Oncorhynchus mykiss) were, respectively, exposed for 96 h to intracellular and extracellular microcystins (0, 20, and 100 µg L-1) produced by Microcystis aeruginosa. Fish were dissected at 24 h intervals for histopathology, targeted microcystin quantification, and nontargeted proteomics. Rainbow Trout accumulated intracellular and extracellular microcystins in all tissues within 24 h, with greater accumulation in the extracellular state. Proteomics revealed intracellular and extracellular microcystins caused sublethal toxicity by significantly dysregulating proteins linked to the cytoskeletal structure, stress responses, and DNA repair in all tissues. Pyruvate metabolism in livers, anion binding in kidneys, and myopathy in muscles were also significantly impacted. Histopathology corroborated these findings with evidence of necrosis, apoptosis, and hemorrhage at similar severity in both microcystin treatments. We demonstrate that sublethal concentrations of intracellular and extracellular microcystins cause adverse effects in Rainbow Trout after short-term exposure.


Assuntos
Cianobactérias , Microcystis , Oncorhynchus mykiss , Animais , Água Doce , Proliferação Nociva de Algas , Microcistinas/toxicidade
15.
Ecotoxicol Environ Saf ; 222: 112508, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34284326

RESUMO

This study determined time-dependent IC50 and confirmed 3.5 mg/L as IC50 value for kaempferol inhibiting toxigenic Microcystis growth, based on which algicidal effects and mechanisms against toxigenic Microcystis exposed to various kaempferol doses (0.5-2 × IC50) were explored along 14 day-test. Results showed that growth inhibition ratio (GIR) almost elevated with increasing kaempferol dose, and at each dose GIR elevated firstly and fluctuated around 17.8%- > 40%, 53.6%-65.6% and 84.8%-89.3% at 1.75, 3.5 and 7 mg/L kaempferol during mid-late stage, respectively. With rising kaempferol dose, photosynthetic pigments contents (chlorophyll-a, phycobiliproteins), antioxidant response (superoxide dismutase and catalase (CAT) activities, glutathione (GSH) contents) and microcystins (MCs) production were almost increasingly stimulated as cellular protective responses during early-mid stage. However, these parameters (excluding CAT and GSH) were almost increasingly inhibited at late stage by prolonged stress and Microcystis cell was still more severely damaged as dose elevated along test, which could be reasons for increasing GIR with rising kamepferol dose. Persistent stimulation of CAT and GSH at each dose could alleviate cell damage until late stage, thus GIR no longer increased at late stage at each kaempferol dose. Moreover, fewer MCs release under kaempferol stress than control suggested kaempferol as eco-safe algaecide for migrating toxigenic Microcystis-dominated blooms (MCBs) and decreasing MCs risks. Compared with our previous data for luteolin inhibiting toxigenic Microcystis, this study supported formerly-proposed 'flavonoids structure - algicidal activity' relationship that the only OH-location difference between kaempferol and luteolin could affect algicidal activity and mechanisms against toxigenic Microcystis. Also, kaempferol and luteolin was revealed to exert additive effect on toxigenic Microcystis growth at equitoxic ratio. Our findings gave novel algicidal scenario of flavonoids and were greatly implicated in eco-friendly migrating toxigenic MCBs.


Assuntos
Microcystis , Antioxidantes , Clorofila A , Quempferóis/farmacologia , Microcistinas/toxicidade , Superóxido Dismutase
16.
Sci Total Environ ; 795: 148864, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34328929

RESUMO

In recent decades, cyanobacteria harmful algal blooms (cyanoHABs) have increased in magnitude, frequency, and duration in freshwater ecosystems. CyanoHABs can impact water quality by the production of potent toxins known as cyanotoxins. Environmental exposure to cyanotoxins has been associated with severe illnesses in humans, domestic animals, and wildlife. However, the effects of sustained exposure to cyanotoxins on aquatic life are poorly understood. In this study, over 150 peer-reviewed articles were critically evaluated to better understand the ecotoxicity of 5 cyanotoxin classes (microcystins, cylindrospermopsin, anatoxin-a, saxitoxins, nodularin) on fish, amphibians, aquatic invertebrates, and birds exclusively feeding in freshwater habitats. The systemic review demonstrated that microcystins, and more specifically microcystin-LR, were the most studied cyanotoxins. Ecotoxicological investigations were typically conducted using a fish or aquatic invertebrate model, with mortality, bioaccumulation, and biochemical responses as the most frequently measured endpoints. After excluding the studies that did not meet our acceptability criteria, remaining studies were examined to identify the no-observed and lowest observed effect concentrations (NOEC and LOEC) for microcystins; the limited amount of data for other cyanotoxins did not allow for analysis. The published ecotoxicity data suggests that the U.S. EPA recreational water quality criteria for microcystin (8 µg/L) may be protective of acute toxicity in aquatic organisms but does not appear to protect against chronic toxicity. Individual U.S. states have developed more stringent recreational health-based thresholds, such as 0.8 µg/L in California. Comparisons of this threshold to the chronic NOEC and LOEC data indicate that more restrictive microcystins thresholds may be required to be protective of aquatic life. Additional research is needed to evaluate the sublethal effects of a wider array of microcystin congeners and other cyanotoxins on organisms relevant to U.S. watersheds to better support nationwide thresholds protective of aquatic life.


Assuntos
Toxinas Bacterianas , Cianobactérias , Animais , Ecossistema , Água Doce/análise , Proliferação Nociva de Algas , Humanos , Microcistinas/toxicidade , Estados Unidos
17.
Toxicon ; 200: 30-37, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34217748

RESUMO

Microcystins (MCs) are hepatotoxic cyanotoxins implicated in several incidents of human and animal toxicity. Microcystin-(Lysine, Arginine) or MC-LR is the most toxic and encountered variant of MCs where oxidative stress plays a key role in its toxicity. This study investigated the oxidative damages induced in the liver and heart of Balb/C mice by an intraperitoneal injected acute dose of MC-LR. Thereafter, the potential protective effect of garlic (Allium sativum) extract supplementation against such damages was assessed through the evaluation of oxidative stress and cytotoxicity markers. Lipid peroxidation (LPO), carbonyl content (CC), glutathione content (GSH), alkaline phosphatase activity (ALP), lactate dehydrogenase (LDH) and sorbitol dehydrogenase (SDH) activities were measured. Results showed important oxidative damages in hepatic and cardiac cells of mice injected with the toxin. However, these damages have been significantly reduced in mice supplemented with garlic extract. Thus, this study demonstrated for the first time the effective use of garlic as an antioxidant agent against oxidative damages induced by MC-LR. As well, this study supports the use of garlic as a potential remedy against pathologies related to toxic agents.


Assuntos
Alho , Microcistinas , Animais , Antioxidantes/metabolismo , Fígado/metabolismo , Toxinas Marinhas , Camundongos , Microcistinas/metabolismo , Microcistinas/toxicidade , Estresse Oxidativo
18.
Sci Total Environ ; 795: 148865, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34246136

RESUMO

Cyanobacterial blooms constitute a global ecological problem that can seriously threaten human health. One of the most common bloom-forming cyanobacteria in freshwater is Microcystis aeruginosa, whose secretion of toxic substances (microcystins, MCs) have strong liver toxicity and endanger the health of exposed people through contaminated aquatic products and drinking water. However, few studies on the neurotoxicity of M. aeruginosa to zebrafish have simulated the process of an actual cyanobacterial bloom. In this study, we used the zebrafish (Danio rerio) as an effective model organism to study the acute neurotoxicity of M. aeruginosa, and to clarify its principal mechanism of action. A total of 82 upregulated and 26 downregulated proteins were detected by quantitative proteomics analysis in zebrafish brain after exposure to M. aeruginosa. Intriguingly, these proteins with changed expression were related to Synaptic vesicle cycle and terpenoid skeleton biosynthesis pathway, such as ACAT, STX1A, and V-ATPase. The obtained results uniformly indicated that the neurotoxicity of M. aeruginosa seriously damaged the neurotransmitter conduction in the nervous system and brain information storage and transmission of zebrafish and makes it more susceptible to neurological diseases. Our study provides a new perspective on the neurotoxicity risk of cyanobacterial blooms.


Assuntos
Microcystis , Peixe-Zebra , Animais , Encéfalo , Água Doce , Humanos , Microcistinas/toxicidade , Proteômica
19.
Ecotoxicol Environ Saf ; 220: 112405, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34130182

RESUMO

Hazardous substances, such as microcystin-LR (MC-LR) and phenanthrene (Phe) are ubiquitous co-contaminants in eutrophic freshwaters, which cause harms to aquatic organisms. However, the risks associated with the co-exposure of aquatic biota to these two chemicals in the environment have received little attention. In this study, the single and mixture toxic effects of MC-LR and Phe mixtures were investigated in Daphnia magna after acute and chronic exposure. Acute tests showed that the median effective concentrations (48 h) for MC-LR, Phe and their mixtures were 13.46, 0.57 and 8.84 mg/L, respectively. Mixture toxicity prediction results indicated that the independent action model was more applicable than the concentration addition model. Moreover, combination index method suggested that the mixture toxicity was concentration dependent. Synergism was elicited at low concentrations of MC-LR and Phe exposure (≤4.04 + 0.17 mg/L), whereas antagonistic or additive effects were induced at higher concentrations. The involved mechanism of antagonism was presumably attributable to the protective effects of detoxification genes activated by high concentrations of MC-LR in mixtures. Additionally, chronic results also showed that exposure to a MC-LR and Phe mixture at low concentrations (≤50 +2 µg/L) resulted in greater toxic effects on D. magna life history than either chemical acting alone. The significant inhibition on detoxification genes and increased accumulation of MC-LR could be accounted for their synergistic toxic effects on D. magna. Our findings revealed the exacerbated ecological hazard of MC-LR and Phe at environmental concentrations (≤50 +2 µg/L), and provided new insights to the potential toxic mechanisms of MC-LR and Phe in aquatic animals.


Assuntos
Daphnia/efeitos dos fármacos , Toxinas Marinhas/toxicidade , Microcistinas/toxicidade , Fenantrenos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Organismos Aquáticos/efeitos dos fármacos , Daphnia/genética , Daphnia/crescimento & desenvolvimento , Daphnia/metabolismo , Interações Medicamentosas , Água Doce/química , Inativação Metabólica/efeitos dos fármacos , Inativação Metabólica/genética , Estágios do Ciclo de Vida/efeitos dos fármacos , Toxinas Marinhas/análise , Microcistinas/análise , Fenantrenos/análise
20.
Ecotoxicol Environ Saf ; 221: 112438, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34175825

RESUMO

Microcystin-leucine arginine (MCLR), a widespread environmental contaminant produced by cyanobacteria, poses a severe threat to the male reproductive system. However, the mechanisms of MCLR-induced testis injury accompanied by autophagy are still obscure. This study aimed to investigate the effects of MCLR on autophagy and apoptosis on the male reproductive system and its mechanism both in vitro and in vivo. MCLR caused damage to the testis of zebrafish, resulting in decreased hatching and growth retardation in the offspring. It also remarkably enhanced autophagic flux by elevating the expression of LC3BII, ATG5, and ATG12 proteins. The autophagic flux was also confirmed through the formation of autophagosomes in the ultrastructure of the zebrafish testis and the accumulation of LC3-positive puncta in zebrafish testis and mouse TM4 cells. Further evaluations revealed that inhibition of autophagy by 3-methyladenine (3-MA) significantly attenuated MCLR-induced apoptosis. This finding indicated that autophagy plays an essential role in cell death in the male reproductive system. Besides, inhibiting endoplasmic reticulum (ER) stress using 4-phenylbutyrate (4-PBA) remarkably blocked autophagy and partially suppressed apoptosis in TM4 cells induced by MCLR. This phenomenon suggested that ER stress-related autophagy was involved in MCLR-induced apoptosis. This study reveals crosstalk between ER stress and autophagy via the PERK/eIF2α/ATF4 signaling pathway. It further suggests that ER stress-related autophagy contributes to MCLR-induced apoptosis and injury in the male reproductive system. These findings provide a novel insight into MCLR-induced impairments of the testis.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Microcistinas/toxicidade , Testículo/efeitos dos fármacos , Animais , Autofagossomos/metabolismo , Autofagossomos/ultraestrutura , Linhagem Celular , Masculino , Camundongos , Fenilbutiratos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Testículo/ultraestrutura , Peixe-Zebra
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