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1.
Sci Total Environ ; 750: 141569, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32853936

RESUMO

Although the long-term exposure of aquatic organisms to cyanobacterial blooms is a regular occurrence in the environment, the prooxidant and neurotoxic effects of such conditions are still insufficiently investigated in situ. We examined the temporal dynamics of the biochemical parameters in the liver of Pelophylax kl. esculentus frogs that inhabit the northern (N) side of Lake Ludas (Serbia) with microcystins (MCs) produced in a cyanobacterial bloom over three summer months. The obtained data were compared with data on frogs that live on the southern (S), MC-free side of the same lake. Our results showed that the MC-producing bloom induced oxidative damage to proteins and lipids, observed as a decrease in the concentration of protein -SH groups and increased lipid peroxidation (LPO) in the liver of N frogs in comparison to S frogs. Glutathione (GSH) played a key role in the transient defense against the MC-induced development of LPO. The low glutathione peroxidase (GPx) activity detected in all groups of frogs from the N site was crucial for the observed prooxidant consequences. The bloom impaired cholinergic homeostasis as a result of a decrease in ChE activity. A delayed neurotoxic effect in relation to the prooxidant outcomes was observed. Our results also showed that even though the integrated biomarker response (IBR) of the antioxidant biomarkers increased during exposure, the individual biochemical parameters did not exhibit a well-defined time-dependent pattern because of specific adaptation dynamics and/or additional effects of the physicochemical parameters of the water. This comprehensive environmental ecotoxicological evaluation of the cyanobacterial bloom-induced biochemical alterations in the liver of frogs provides a new basis for further investigations of the prolonged, real-life ecotoxicity of the blooms.


Assuntos
Cianobactérias , Microcistinas , Animais , Cianobactérias/metabolismo , Fígado/metabolismo , Microcistinas/metabolismo , Microcistinas/toxicidade , Estresse Oxidativo , Rana esculenta/metabolismo , Sérvia
2.
Ecotoxicol Environ Saf ; 203: 110994, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888603

RESUMO

The effects of cyanobacteria (Aphanizomenon flos-aquae (90%), Microcystis aeruginosa) and dense Elodea canadensis beds on the health endpoints of the amphipod Gmelinoides fasciatus and bivalve mollusc Unio pictorum were examined in mesocosms with simulated summer conditions (July-August 2018) in the environment of the Rybinsk Reservoir (Volga River Basin, Russia). Four treatments were conducted, including one control and three treatments with influencing factors, cyanobacteria and dense elodea beds (separately and combined). After 20 days of exposure, we evaluated the frequency of malformed and dead embryos in amphipods, heart rate (HR) and its recovery (HRR) after stress tests in molluscs as well as heat tolerance (critical thermal maximum or CTMax) in both amphipods and molluscs. The significant effect, such as elevated number of malformed embryos, was recorded after exposure with cyanobacteria (separately and combined with elodea) and presence of microcystins (MC) in water (0.17 µg/l, 40% of the most toxic MC-LR contribution). This study provided evidence that an elevated number (>5% of the total number per female) of malformed embryos in amphipods showed noticeable toxicity effects in the presence of cyanobacteria. The decreased oxygen under the influence of dense elodea beds led to a decrease in HR (and an increase in HRR) in molluscs. The notable effects on all studied biomarkers, embryo malformation frequency and heat tolerance in the amphipod G. fasciatus, as well as the heat tolerance and heart rate in the mollusc U. pictorum, were found when both factors (elodea and cyanobacteria) were combined. The applied endpoints could be further developed for environmental monitoring, but the obtained results support the importance of the combined use of several biomarkers and species, especially in the case of multi-factor environmental stress.


Assuntos
Anfípodes/efeitos dos fármacos , Bivalves/efeitos dos fármacos , Cianobactérias/metabolismo , Monitoramento Ambiental/métodos , Hydrocharitaceae/metabolismo , Poluentes Químicos da Água/toxicidade , Anfípodes/metabolismo , Animais , Aphanizomenon/metabolismo , Biomarcadores/análise , Bivalves/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Microcistinas/metabolismo , Microcistinas/toxicidade , Microcystis/metabolismo , Federação Russa , Poluentes Químicos da Água/metabolismo
3.
Ecotoxicology ; 29(9): 1347-1357, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32772242

RESUMO

Gut microbiota has been shown to play critical roles in host health. The present study was to determine the toxicological effects of microcystin-LR (MCLR) on gut microbial community and metabolites using 16S rDNA sequencing and gas chromatography-mass spectrometry (GC-MS). MCLR was administered to BALB/c mice by gavage for eight weeks. Results of the microbial alpha-diversity (Sobs, Chao1, ACE and Shannon indexes) decreased in MCLR-treated group versus controls. Phylum Candidatus Saccharibacteria decreased significantly in MCLR-treated group versus controls. Correspondingly, more than thirties genera in relative abundance decreased, especially short chain fatty acid (SCFA)-producing bacteria (e.g., Alistipes and Ruminococcus). These results indicated that the gut microbial community structure was remarkably changed by MCLR. Furthermore, concentrations of SCFAs were significantly decreased after MCLR exposure (P < 0.01), where butyrate decreased as high as 4.9-fold. Consequently, sub-chronic exposure to MCLR could not only alter the microbial composition but metabolites. This study offered novel insights into the toxic mechanism of MCs from gut microbiota, and facilitated further clarification of risks to human health from MCs exposure.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Microcistinas/toxicidade , Animais , Biodiversidade , Ácidos Graxos Voláteis/metabolismo , Camundongos , Camundongos Endogâmicos BALB C
4.
Toxicon ; 186: 151-159, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32798503

RESUMO

Heavy metals and microcystins commonly co-exist in water bodies with cyanobacteria, and have been shown to affect aquatic plants. However, their combined effects remain largely unknown. In this study, the toxic effects of copper (Cu) and cadmium (Cd) on Ceratophyllum demersum L. were characterized in the presence of microcystin-LR (MC-LR). The results showed that the bioaccumulation of MC-LR and Cu/Cd in C. demersum was significantly increased by the interaction between MC-LR and Cu/Cd. The combined toxicity assessment results suggested that the toxicities of Cu or Cd to C. demersum would be largely exacerbated by MC-LR, which could be the results of increased bioaccumulation of the pollutants. Cu, Cd and MC-LR, as well as their mixture, significantly decreased plant fresh weight and total chlorophyll content of C. demersum, especially at their high concentrations. The antioxidative system was activated to cope with the adverse effects of oxidative stress. Antioxidant enzyme activities were significantly stimulated by Cu, Cd and MC-LR, as well as their mixture. However, the decreased superoxide dismutase (SOD) and glutathione reductase (GR) activities were observed when exposed to relative high concentrations of Cu or Cd together with MC-LR of 5 µg L-1. MC-LR brought more stress to the antioxidative system, which is another possible explanation for the synergistic effect. Our findings highlight increased ecological risks of the co-contamination of heavy metals and harmful cyanobacteria.


Assuntos
Cádmio/toxicidade , Cobre/toxicidade , Microcistinas/toxicidade , Traqueófitas/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Organismos Aquáticos/efeitos dos fármacos , Traqueófitas/fisiologia
5.
Bull Environ Contam Toxicol ; 105(2): 337-344, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32676683

RESUMO

This study explored nitrogen (N)-dependent interaction between Microcystis and chloramphenicol (CAP) along 20 day-test. Results showed that 5 mg/L N largely alleviated inhibitory effects of CAP on Microcystis growth, while 50 and 0.5 mg/L N exacerbated growth-inhibition by CAP especially in early (before day 8) and mid-late stage, respectively. At each N level, CAP-induced antioxidant defense and cell damage extents were negatively correlated to growth state in each stage, and CAP-biodegradation coincided with Microcystis growth and glutathione synthesis dynamics, implying that antioxidant defense, cell damage and CAP-removal closely linked to N-dependent Microcystis growth under CAP-stress. Microcystin (MC)-production and -release under CAP-stress were also N-dependent. Although Microcystis growth was greatly-inhibited by prolonged CAP-stress at 0.5 mg/L N, delayed CAP-loss and high MC-release at 0.5 mg/L N should be emphasized during Microcystis-dominated cyanobacterial blooms (MCBs) and CAP co-occurrence. This study had great implication in risk assessment for MCBs-CAP co-occurrence in different waters.


Assuntos
Cloranfenicol/toxicidade , Microcistinas/toxicidade , Microcystis , Cianobactérias/metabolismo , Nitrogênio/metabolismo
6.
Aquat Toxicol ; 225: 105526, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32569999

RESUMO

Microcystin (MC) is a cyclic heptapeptide toxin. Nuclear factor erythocyte 2-related factor 2 (Nrf2) can enhance cellular survival by mediating phase 2 detoxification and antioxidant genes. In this study, CpNrf2 cDNA sequences were cloned from freshwater bivalve Cristaria plicata. The full-length CpNrf2 cDNA sequence was 4259 bp, and its homology was the highest with Mizuhopecten yessoensis, reaching 46%. CpNrf2 transcription levels were examined in all tested tissues, and the highest level was in hepatopancreas from C. plicata. The recombinant protein pET32-CpNrf2 was purified with the content of 1.375 mg/mL. The expression levels of CpNrf2 mRNA were raised in hepatopancreas after MC stimulation. After CpNrf2 knockdown, CpNrf2 mRNA levels were significantly down-regulated after 24 h. Compared with control group, the expression levels of ARE-driven enzymes (CpMnSOD, CpCuZnSOD, CpTRX, CpPrx, CpSe-GPx and Cpsigma-GST) were significantly increased, and those enzyme activities were also significantly up-regulated in MC-stimulated group. However, in CpNrf2-iRNA group, they were significantly down-regulated. The results revealed that Nrf2/ARE pathway is very crucial to protect molluscs from MC.


Assuntos
Antioxidantes/metabolismo , Expressão Gênica/efeitos dos fármacos , Microcistinas/toxicidade , Fator 2 Relacionado a NF-E2/genética , Unionidae/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , Filogenia , Proteínas Recombinantes/genética , Unionidae/enzimologia , Unionidae/genética
7.
Chemosphere ; 257: 127111, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32485513

RESUMO

Microcystin-leucine arginine (MC-LR) is a potent liver toxin produced by freshwater cyanobacteria, also known as blue-green algae. While harmful algal blooms are increasing in frequency and severity worldwide, there is still no established method for the diagnosis and assessment of MC-LR induced liver damage. The guidelines for MC-LR safe exposure limits have been previously established based on healthy animal studies, however we have previously demonstrated that pre-existing non-alcoholic fatty liver disease (NAFLD) increases susceptiblity to the hepatotoxic effects of MC-LR. In this study, we sought to investigate the suitability of clinically used biomarkers of liver injury, specifically alanine aminotransferase (ALT) and alkaline phosphatase (ALP), as potential diagnostic tools for liver damage induced by chronic low dose administration of MC-LR in the setting of pre-existing NAFLD. In our Leprdb/J mouse model of NAFLD, we found that while MC-LR induced significant histopathologic damage in the setting of NAFLD, gene expression of ALT and ALP failed to increase with MC-LR exposure. Serum ALT and ALP also failed to increase with MC-LR exposure, except for a moderate increase in ALP with the highest dose of MC-LR used (100 µg/kg). In HepG2 human liver epithelial cells, we observed that increasing MC-LR exposure levels do not lead to an increase in ALT or ALP gene expression, intracellular enzyme activity, or extracellular activity, despite a significant increase in MC-LR induced cytotoxicity. These findings demonstrate that ALT and ALP may be unsuitable as diagnostic biomarkers for MC-LR induced liver damage.


Assuntos
Fígado/metabolismo , Microcistinas/toxicidade , Alanina Transaminase/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cianobactérias , Expressão Gênica , Proliferação Nociva de Algas , Humanos , Camundongos , Hepatopatia Gordurosa não Alcoólica
8.
Chemosphere ; 256: 127157, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32470740

RESUMO

Microcystins released by cyanobacteria affect crop growth and productivity, and even food safety. Plant hormones play a vital role in regulating growth, development and stress response in plants. Therefore, we studied the response of hormones including abscisic acid (ABA), indole-3-acetic acid (IAA), Zeatin (ZT) and gibberellin (GA3) as well as hormone balances (IAA/ABA, ZT/ABA and GA/ABA) to cyanobacterial extract containing microcystins (1, 10, 100 and 1000 µg/L) during stress and recovery periods. Low concentration microcystins (1 µg/L) promoted growth of rice seedlings by increasing levels of IAA, ZT and GA3 and maintaining hormone balances. In addition, the up-regulation of OsYUCCA1 increased IAA level in rice roots by promoting IAA biosynthesis. High concentrations microcystins (10, 100 or1000 µg/L) inhibited growth of rice seedlings by reducing levels of IAA, ZT and GA3 and ratios of IAA/ABA, ZT/ABA and GA/ABA due to increased ABA level. The increase in ABA in rice seedlings induced by high concentrations MCs was resulted from up-regulation of OsNCED1, OsNCED3, OsNCED4 and OsZEP to enhance ABA biosynthesis, and was controlled by up-regulating expression levels of OsABAox1-3 for enhancing ABA catabolism as negative feedback. The highest concentration of MCs (1000 µg/L) caused irreversible damage to metabolisms of IAA and ABA, partly resulting in unrecoverable inhibition on rice growth. All results demonstrate that "low-concentration promotion and high-concentration inhibition" of microcystins was associated with changes in hormone levels and balances by affecting their metabolisms, and could be helpful for guiding agricultural irrigation with microcystin contaminated water.


Assuntos
Cianobactérias/metabolismo , Microcistinas/toxicidade , Oryza/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Plântula/metabolismo , Ácido Abscísico/metabolismo , Giberelinas/metabolismo , Ácidos Indolacéticos/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/microbiologia , Extratos Vegetais , Raízes de Plantas/metabolismo , Zeatina/metabolismo
9.
Chemosphere ; 254: 126716, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32334246

RESUMO

Cyanobacteria are prokaryotes involved in the contamination of aquatic environments since they release toxins that are highly potent and dangerous for living organisms. Prokaryotes produce endo and exotoxins, among others. Exotoxins are highly toxic, while endotoxins have milder toxic effects. The present study evaluated the cytotoxicogenetic potency of both toxins studying them in different concentrations of cyanobacterial biomasses (1 µg/L, 1.5 µg/L, 2 µg/L), to assess the amount of exotoxin present in the cultured medium in which the cyanobacteria were grown. For this evaluation, we used an extract taken from the medium in a concentration of 10%. Our results showed that genotoxic and mutagenic changes in Allium cepa could be observed in all of the varying concentrations of biomass (endotoxin action) and also in the medium induced with exotoxin. Even at low concentrations, these toxins were highly effective at triggering changes in the DNA molecules of organisms exposed to them. This information is highly significant when considering environmental contamination caused by cyanobacteria blooms, since the results of this study show that these toxins may not only kill organisms when found in high concentrations, but also induce mutations when found in low concentrations. Since these mutations are expressed later on in the organisms, it is impossible to associate the observed effect with the event that induced the damage.


Assuntos
Cianobactérias/patogenicidade , Dano ao DNA , Endotoxinas/toxicidade , Exotoxinas/toxicidade , Biomassa , Microcistinas/toxicidade , Mutagênicos/toxicidade , Cebolas/efeitos dos fármacos
10.
Artigo em Inglês | MEDLINE | ID: mdl-32277321

RESUMO

Understanding the growth and development of aquatic plants in eutrophic water is of great significance for the selection of potential candidate plant for use in the phytoremediation of eutrophic aquatic ecosystems. The present study aimed to investigate the chronic effects of microcystin-LR (MC-LR) on photosynthesis in the leaves of Typha angustifolia Linn. Photosynthetic activity was stimulated in the leaves following exposure to 4.6 µg L-1 MC-LR for six weeks based on the enhancement of Ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) activity and net photosynthetic rate (PN). However, PN decreased significantly after exposure to 49.1 or 98.3 µg L-1 MC-LR, via non-stomatal limitation by reducing the chlorophyll a and b contents and Rubisco activity. In addition, glycolate oxidase (GO) and serine:glyoxylate aminotransferase (SGAT) activities decreased significantly, indicating that the photorespiration pathway was affected adversely. The intercellular carbon dioxide (Ci) concentration decreased significantly following exposure to 98.3 µg L-1 MC-LR, accompanied with decreases in PN and stomatal conductivity (gs), indicating that stomatal limitation on the photosynthesis system in T. angustifolia L. was observed after exposure to 98.3 µg L-1 MC-LR. Under long-term exposure to MC-LR (49.1-98.3 µg L-1), oxidation stress was severe in the aquatic plant, and non-stomatal limitation or stomatal limitation effects on the photosynthesis system were obvious, resulting in decreases in photosynthesis rates.


Assuntos
Microcistinas/toxicidade , Fotossíntese/efeitos dos fármacos , Typhaceae/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Antioxidantes , Clorofila A , Ecossistema , Estresse Oxidativo , Folhas de Planta , Ribulose-Bifosfato Carboxilase/metabolismo , Testes de Toxicidade Crônica , Typhaceae/fisiologia , Água
11.
Ecotoxicol Environ Saf ; 194: 110444, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32169726

RESUMO

Nodularin (NOD) is a kind of cyanobacterial toxins. It is of concern due to elicit severe genotoxicity in humans and animals. The comprehensive evaluation of NOD-induced adverse effects in living organisms is urgently needed. This study is aimed to report the developmental toxicity and molecular mechanism using zebrafish embryos exposed to NOD. The embryonic toxicity induced by NOD is demonstrated by inhibition of embryo hatching, increase in mortality rate, abnormal heart rate, embryonic malformation as well as defects in angiogenesis and common cardinal vein remodeling. NOD triggered a decreased rate of angiogenesis through inhibiting endothelial cells migration. NOD induced embryonic cell apoptosis and DNA damage, which can be alleviated by antioxidant N-acetyl-L-cysteine. NOD significantly caused oxidative damage as indicated by changes in reactive oxygen species, superoxide dismutase, catalase, glutathione and malondialdehyde. NOD also altered the expression of vascular development-genes (DLL4, CDH5, VEGFA, VEGFC) and apoptosis-related genes (BAX, BCL-2, P53, CASPASE 3). Taken together, NOD induced adverse effect on zebrafish embryos development, which may be associated with oxidative stress and apoptosis through the activation of P53-BAX/BCL-2-CASPASE 3-mediated pathway.


Assuntos
Toxinas Bacterianas/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Toxinas Marinhas/toxicidade , Microcistinas/toxicidade , Peptídeos Cíclicos/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Dano ao DNA , Células Endoteliais/metabolismo , Humanos , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra/metabolismo
12.
PLoS Negl Trop Dis ; 14(3): e0008060, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163415

RESUMO

The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak took place in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water supplies of NE compared to other regions of Brazil. Experimentally, we described that STX doubled the quantity of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms.


Assuntos
Morte Celular/efeitos dos fármacos , Microcefalia/patologia , Envenenamento/complicações , Envenenamento/patologia , Saxitoxina/toxicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/patologia , Animais , Toxinas Bacterianas/análise , Toxinas Bacterianas/toxicidade , Encéfalo/patologia , Brasil/epidemiologia , Células Cultivadas , Modelos Animais de Doenças , Surtos de Doenças , Feminino , Humanos , Incidência , Toxinas Marinhas/análise , Toxinas Marinhas/toxicidade , Camundongos Endogâmicos C57BL , Microcistinas/análise , Microcistinas/toxicidade , Modelos Teóricos , Neurotoxinas/análise , Neurotoxinas/toxicidade , Saxitoxina/análise , Água/química
13.
PLoS One ; 15(3): e0229148, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160215

RESUMO

Lake Lesser Prespa in Greece is a vital breeding habitat for the Dalmatian and Great White Pelican and a shelter for numerous rare and endemic species. However, eutrophication processes are distressing the lake system and the outbreaks of cyanobacterial blooms during the warm months may pose a threat to aquatic organisms due to the presence of microcystins (MCs). In this study we hypothesize that nutrients (eutrophication), nutrient-rich pelican droppings (guanotrophication) and warming (climate change) can affect the algal growth and MCs production in the water layer of Lake Lesser Prespa. Seston collected from three lake sites was incubated at ambient (20°C) and high (30°C) temperature with or without the addition of nutrients (nitrogen (N), phosphorus (P)), or pelican droppings. Results showed increased chlorophyll-a at higher temperature (30°C). N addition yielded higher chlorophyll-a levels than the non-treated water or when only P was added. The addition of both N and P as well as the addition of pelican dropping resulted in the highest chlorophyll-a at both temperatures. Notably, in the dropping-treatments, cyanobacteria and MCs were promoted while changes were evoked in the relative contribution of toxic MC-variants. Guanotrophication may thus influence the cyanobacterial dynamics and most likely their toxicity profile at Lesser Prespa.


Assuntos
Clorófitas , Mudança Climática , Cianobactérias , Eutrofização , Lagos , Microcistinas/metabolismo , Animais , Aves/metabolismo , Clorófitas/crescimento & desenvolvimento , Clorófitas/metabolismo , Cianobactérias/crescimento & desenvolvimento , Cianobactérias/metabolismo , Fezes , Grécia , Microcistinas/toxicidade , Temperatura
14.
Ecotoxicol Environ Saf ; 195: 110408, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32179236

RESUMO

Microcystin-LR (MC-LR) is a widely known hepatotoxin which could induce the occurrence and metastasis of hepatocellular carcinoma. In recent years, with the frequent outbreak of cyanobacteria, the harm of MC-LR has gradually attracted more attention. Hence, this study focused on the effect of MC-LR on DNA damage in HepG2 cells, identifying the types and sources of free radicals that make an important function on this issue. Our data suggested that MC-LR induced concentration- and time-dependent increasement of DNA double-strand breaks (DSBs). After exposure to 1 µM MC-LR for 3 days, the protein expression and immunofluorescence staining of γ-H2AX was significantly increased. Using a scavenger of mitochondrial O2.- (4-hydroxy-tempo), a inhibitor of mitochondrial NOS (7-nitroindazole), and a scavenger of ONOO- (uric acid), it was revealed that ONOO- originated from mitochondria made a significant contribution to the genotoxicity of MC-LR. Moreover, a significant decreasement of mitochondrial membrane potential (MMP) was observed. These findings suggested that peroxynitrite targeting mitochondria plays a vital role in the MC-LR-induced genotoxic response in mammalian cells.


Assuntos
Quebras de DNA de Cadeia Dupla , Microcistinas/toxicidade , Mitocôndrias Hepáticas/efeitos dos fármacos , Ácido Peroxinitroso/metabolismo , Animais , Carcinoma Hepatocelular/genética , Cianobactérias/crescimento & desenvolvimento , Células Hep G2 , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/genética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo
15.
Toxicol Lett ; 326: 106-113, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32142839

RESUMO

This study aimed to investigate the toxic effects of microcystin-LR (MC-LR), which is released from several bloom-forming cyanobacteria, on the glucose metabolism of pancreatic ß cells in vivo and in vitro. Male mice and the pancreatic MIN6 cells were respectively treated with varying concentrations of MC-LR. After 3- or 6- months of MC-LR exposure, increase in the body weight of mice was found to be inhibited, and the structure of their pancreatic tissues was damaged with impaired glucose tolerance and impaired insulin secretion. Further, these toxic effects became more pronounced with time and with increased dosages. Direct cytotoxic effects of MC-LR were observed in the MIN6 pancreatic ß-cells possibly due to their expression of the MC-LR specific transporter. MC-LR entered the MIN6 cells that significantly reduced the cell viability. Both in vivo and in vitro experiments demonstrated that MC-LR was able to induce apoptosis, possibly associated with mitochondrial damage. Above all, these findings implied that MC-LR may be transported into the pancreatic ß cells and cause subsequent cytotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cianobactérias/química , Glucose/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Microcistinas/toxicidade , Pâncreas/efeitos dos fármacos , Animais , Masculino , Camundongos
16.
Environ Toxicol ; 35(8): 822-830, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32170997

RESUMO

Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide hepatotoxin produced by cyanobacteria. MicroRNA-122 (miR-122) is specifically expressed in the liver. This study focuses on the role of miR-122 in MC-LR-induced dysregulation of hepatic iron homeostasis in C57BL/6 mice. The thirty mice were randomly divided into five groups (Control, 12.5 µg/kg·BW MC-LR, 25 µg/kg·BW MC-LR, Negative control agomir and 25 µg/kg·BW MC-LR + miR-122 agomir). The results show that MC-LR decreases the expressions of miR-122, Hamp, and its related regulators, while increasing the content of hepatic iron and the expressions of FPN1 and Tmprss6. Furthermore, miR-122 agomir pretreatment improves MC-LR induced dysregulation of hepatic iron homeostasis by arousing the related regulators and reducing the expression of Tmprss6. These results suggest that miR-122 agomir can prevent the accumulation of hepatic iron induced by MC-LR, which may be related to the regulation of hepcidin by BMP/SMAD and IL-6/STAT signaling pathways.


Assuntos
Microcistinas/toxicidade , Testes de Toxicidade , Animais , Arginina , Hepcidinas , Homeostase , Ferro , Leucina , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo
17.
Environ Int ; 138: 105648, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32187572

RESUMO

Microcystins (MCs) produced by cyanobacteria pose serious threats to human health. However, the contribution of long-term exposure to MCs to the development of nonalcoholic fatty liver disease (NAFLD) remains poorly documented. In this study, we estimated the environmental uptake of MCs by a small population of fishers who have lived for many years on Meiliang Bay of Lake Taihu, where cyanobacterial blooms occur frequently. Serum biochemical indices of liver function and their relationships with MC contamination in these people were also investigated. Moreover, to mimic the long-term effects of MC on the livers of fishers, an animal model was established in which mice were exposed to MC-LR at an environmentally relevant level, a reference level (the no-observed adverse effect level, NOAEL), and three times the NOAEL through drinking water for 12 months. We estimated the total daily intake of MCs by fishers through contaminated lake water and food to be 5.95 µg MC-LReq, far exceeding the tolerable daily intake (2.40 µg MC-LReq) proposed by the World Health Organization (WHO). More than 80% of participants had at least one abnormal serum marker. The indices of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), triglyceride (TG), globulin (GLB), and lactate dehydrogenase (LDH) had close positive associations with MC contamination, indicating that both liver damage and lipid metabolism dysfunction were induced by chronic MC exposure. Furthermore, the animal experimental results showed that long-term exposure to MC-LR at the environmentally relevant level led to hepatic steatosis with molecular alterations in circadian rhythm regulation, lipid metabolic processes, and the cell cycle pathway. Exposure to MC-LR at or above the NOAEL worsened the pathological phenotype towards nonalcoholic steatohepatitis disease (NASH) or fibrosis. These results suggest that prolonged exposure to the reference level (NOAEL) of MC-LR could cause severe liver injury to mammals. People with long-term environmental exposure to MCs might be at high risk for developing NAFLD.


Assuntos
Cianobactérias , Hepatopatia Gordurosa não Alcoólica , Animais , Modelos Animais de Doenças , Exposição Ambiental/efeitos adversos , Humanos , Fígado/química , Camundongos , Microcistinas/análise , Microcistinas/toxicidade , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente
18.
Environ Toxicol ; 35(7): 727-737, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32073747

RESUMO

Our previous work indicated exposure of Human liver cell 7702 (HL7702) cells to Microcystin-leucine-arginine (MC-LR) for 24 hours can disrupt insulin (INS) signaling by the hyperphosphorylation of specific proteins. For further exploring the time-dependent effect posed by MC-LR on this pathway, in the current study, HL7702 cells together with mice were exposed to the MC-LR with different concentrations under short-term treatment, and then, protein phosphatase 2A (PP2A) activity and expression of proteins related to INS signaling, as well as the characteristics of their action in the liver, were investigated. The results indicated, in HL7702 cells with 0.5, 1, and 6 hours of treatment by MC-LR, PP2A activity showed an obvious decrease in a time and concentration-dependent manner. While the total protein level of Akt, glycogen synthase kinase 3 (GSK-3), and glycogen synthase remained unchanged, GSK-3 and Akt phosphorylation increased significantly. In livers of mice with 1 hour of intraperitoneal injection with MC-LR, a similar change in these proteins was observed. In addition, the levels of total IRS1 and p-IRS1 at serine sites showed decreasing and increasing trends,respectively, and the hematoxylin and eosin staining showed that liver tissues of mice in the maximum-dose group exhibited obvious hepatocyte degeneration and hemorrhage. Our results further proved that short-term treatment with MC-LR can inhibit PP2A activity and disrupt INS signaling proteins' phosphorylation level, thereby interfering with the INS pathway. Our findings provide a helpful understanding of the toxic effects posed by MC-LR on the glucose metabolism of liver via interference with the INS signaling pathway.


Assuntos
Insulina/metabolismo , Fígado/efeitos dos fármacos , Microcistinas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Glicogênio Sintase/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Fosforilação/efeitos dos fármacos , Proteína Fosfatase 2/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
Environ Toxicol ; 35(7): 738-746, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32061150

RESUMO

Microcystins (MCs), as the most dominant bloom-forming strains in eutrophic surface water, can induce hepatotoxicity by oxidative stress. Alpha-lipoic acid (α-LA) is a super antioxidant that can induce the synthesis of antioxidants, such as glutathione (GSH), by nuclear factor erythroid 2-related factor 2 (Nrf2). However, the potential molecular mechanism of α-LA regeneration of GSH remains unclear. The present study aimed to investigate whether α-LA could reduce the toxicity of MCs induced in human hepatoma (HepG2), Bel7420 cells, and BALB/c mice by activating Nrf2 to regenerate GSH. Results showed that exposure to 10 µM microcystin-leucine arginine (MC-LR) reduced viability of HepG2 and Bel7402 cells and promoted the formation of reactive oxygen species (ROS) compared with untreated cells. Moreover, the protection of α-LA included reducing the level of ROS, increasing superoxide dismutase activity, and decreasing malondialdehyde. Levels of reduced glutathione (rGSH) and rGSH/oxidized glutathione were significantly increased in cells cotreated with α-LA and MC-LR compared to those treated with MC-LR alone, indicating an ability of α-LA to attenuate oxidative stress and MC-LR-induced cytotoxicity by increasing the amount of rGSH. α-LA can mediate GSH regeneration through the Nrf2 pathway under the action of glutathione reductase in MC-LR cell lines. Furthermore, the data also showed that α-LA-induced cytoprotection against MC-LR is associated with Nrf2 mediate pathway in vivo. These findings demonstrated the potential of α-LA to resist MC-LR-induced oxidative damage of liver.


Assuntos
Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glutationa/metabolismo , Microcistinas/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Ácido Tióctico/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Glutationa Redutase/metabolismo , Células Hep G2 , Humanos , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
20.
Toxicon ; 176: 47-54, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32103795

RESUMO

Cyanobacteria species are sensitive to many plant allelochemicals, such as pyrogallol. However, little attention has been paid to the relative effects of these xenobiotics on co-occurring toxigenic and non-toxigenic cyanobacterial strains, despite their co-existence in blooms. Hence, the responses of one toxigenic (TS2) and two non-toxigenic (NS1, NS2) Microcystis aeruginosa strains to pyrogallol were tested under three conditions: mono-culture and co-cultured either directly or separately by dialysis membrane. The study showed that the inhibitory effects of pyrogallol on the growth and photosynthetic yield (Fv/Fm) of either toxigenic or non-toxigenic M. aeruginosa strains were lower in direct and dialysis co-culture conditions than those in mono-culture conditions. This result indicated that chemical-mediated reciprocal effects occur between the co-existing toxigenic and non-toxigenic strains. The toxigenic M. aeruginosa strain was more sensitive to pyrogallol than the non-toxigenic strains in both mono- and co-culture systems, though whether this outcome is due to the former's toxigenic status is unclear. Intracellular microcystin-LR (MC-LR) concentrations of the toxigenic strain decreased after pyrogallol addition in both mono- and co-culture systems, whereas extracellular MC-LR concentrations increased. This finding may reflect the cell damage of M. aeruginosa because of the pyrogallol. At the same initial number of cells, the extracellular MC-LR concentration released from the same amount of TS2 cells in mono-culture was slightly higher than that in dialysis co-culture conditions. Overall, this study shows that plant allelochemicals may have the potential to reduce bloom toxicity by reducing the proportion of toxigenic cyanobacterial strains, and the effects of co-existing strains must be considered when assessing the effects of plant allelochemicals on target strains.


Assuntos
Microcistinas/toxicidade , Microcystis/efeitos dos fármacos , Pirogalol/toxicidade , Cianobactérias , Microcystis/fisiologia , Microbiologia da Água
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