microcystin-LR Research Articles

The new fate of MCLR revealed by dialysis equilibrium and theoretical calculations: Influence from DOM and Fe(II)/Mn(II)

Microcystin-LR (MCLR) is a highly toxic pollutant widely distributed in eutrophic waters. The interplay between dissolved organic matter (DOM) and metal ions has been extensively reported; however, the impact of DOM-metal complexes on MCLR remains to be thoroughly studied. In this research, equilibrium dialysis was employed to study the kinetics and isotherms of MCLR adsorption by DOM, meanwhile the Density functional theory (DFT) calculations provided insights into the theoretical mechanisms of Fe(II)/Mn(II) involvement in the adsorption process. The adsorption kinetics revealed that the process is physicochemical, with chemisorption being the critical factor controlling the adsorption rate. The adsorption isotherms confirmed that Fe(II) alters the spatial arrangement of adsorption sites on the superficies of DOM, with the complexes of Fe(II) and DOM from the macrophyte-dominated regions of Lake Taihu (MDR-Fe(II)) showing the uppermost adsorption capacity of 6193.965 µg/g among all combinations. The influence of different cations (K+, Ca2+, Na+, Mg2+) on the adsorption of MCLR to DOM is divergent, with metals either reducing MCLR adsorption through competition for adsorption sites or increasing it by forming ternary complexes. The pH decrease reduced the affinity of DOM to metal ions while simultaneously enhancing MCLR adsorption through changes in its ionization state. DFT calculations demonstrated that Fe(II)/Mn(II) reduces the resistance to interaction between functional groups on DOM and MCLR, with carboxyl-Fe(II)-carboxyl interactions showing the highest binding energy (ΔG = −7.253 eV). Overall, Fe(II)/Mn(II) enhances the adsorption of MCLR via altering the structure and surface electrostatic potential distribution of DOM. This research indicates that the ultimate fate of MCLR in aquatic ecosystems is affected by DOM and metal ions.

Aerosolized Harmful Algal Bloom Toxin Microcystin-LR Induces Type 1/Type 17 Inflammation of Murine Airways

Harmful algal blooms are increasing globally and pose serious health concerns releasing cyanotoxins. Microcystin-LR (MC-LR), one of the most frequently produced cyanotoxins, has recently been detected in aerosols generated by the normal motions of affected bodies of water. MC-LR aerosol exposure has been linked to a pro-inflammatory influence on the airways of mice; however, little is understood about the underlying mechanism or the potential consequences. This study aimed to investigate the pro-inflammatory effects of aerosolized MC-LR on murine airways. C57BL/6 and BALB/c mice were exposed to MC-LR aerosols, as these strains are predisposed to type 1/type 17 and type 2 immune responses, respectively. Exposure to MC-LR induced granulocytic inflammation in C57BL/6 but not BALB/c mice, as observed by increased expression of cytokines MIP-1α, CXCL1, CCL2, and GM-CSF compared with their respective vehicle controls. Furthermore, the upregulation of interleukins IL-17A and IL-12 is consistent with Th1- and Th17-driven type 1/type 17 inflammation. Histological analysis confirmed inflammation in the C57BL/6 lungs, with elevated neutrophils and macrophages in the bronchoalveolar lavage fluid and increased pro-inflammatory and pro-resolving oxidized lipids. In contrast, BALB/c mice showed no significant airway inflammation. These results highlight the ability of aerosolized MC-LR to trigger harmful airway inflammation, requiring further research, particularly into populations with predispositions to type 1/type 17 inflammation.

Evaluation of Genotoxic and Hemolytic Effects of Aphanizomenon flos-aquae and Microcystis aeruginosa Biomass Extracts on Human Blood Cells In Vitro

This study explores the in vitro effects of cyanotoxins from the methanolic extract of the cyanobacteria Aphanizomenon flos-aquae and Microcystis aeruginosa on human blood cells, with samples drawn from the Gruža reservoir in Serbia. These cyanobacteria, which made up 98.5% of the reservoir’s phytoplankton, reached densities of 4,656,450 cells mL−1, with A. flos aquae (3,105,120 cells mL−1) as the dominant species, followed by M. aeruginosa (1,480,130 cells mL−1). A cyanotoxin analysis of biomass detected anatoxin-a (3.56 µg g−1), cylindrospermopsin (6.86 µg g−1), microcystin LR (0.87 µg g−1), and microcystin RR (2.47 µg g−1). This study assessed the genotoxic potential of the methanolic extract of the cyanobacterial biomass by evaluating the DNA damage and the Genetic Damage Index (GDI) in peripheral blood lymphocytes (PBLs) from healthy donors. The results showed a dose-dependent increase in the DNA damage, from 35.67 ± 4.93% at 10 µg mL−1 to 95.67 ± 1.53% at 100 µg mL−1, with a corresponding rise in the GDI from 0.61 ± 0.02 to 2.39 ± 0.07. The extract also caused the concentration-dependent hemolysis of red blood cells, with 5.63% hemolysis at the highest concentration (200 µg mL−1). These findings underscore the significant genotoxic risks posed by cyanotoxins from biomass extracts of A. flos aquae and M. aeruginosa, particularly in water sources used for human consumption.

Colorimetric aptasensing of microcystin-LR using DNA-conjugated polydiacetylene.

Polydiacetylene (PDA) holds promise as a versatile material for biosensing applications due to its unique optical properties and self-assembly capabilities. In this study, we developed a colorimetric detection biosensor system utilizing PDA and aptamer for the detection of microcystin-LR (MC-LR), a potent hepatotoxin found in cyanobacteria-contaminated environments. The biosensor was constructed by immobilizing MC-LR-specific aptamer on magnetic beads, where the aptamer was hybridized with a urease-labelled complementary DNA (cDNA-urease). Upon binding MC-LR, the aptamer undergoes a conformational change to release cDNA-urease. The released cDNA-urease is subsequently captured by PDA bearing a single-stranded DNA (ssDNA). The enzymatic reaction triggers a distinctive color transition of PDA from blue to red. The results demonstrate exceptional sensitivity, with a linear detection range of 5-100ng/mL and a limit of detection as low as 1ng/mL. The practicability of the colorimetric method was demonstrated by detecting different levels of MC-LR in spiked water samples. The recoveries ranged from 77.3 to 102% and the color change, visible to the naked eye, underscores the practical utility for on-site applications. Selectivity for MC-LR over other microcystin variants (MC-RR and MC-YR) was confirmed. The colorimetric detection platform capitalizes on the properties of PDA and nucleic acid, offering a robust method for detecting small molecules with potential applications in environmental monitoring and public health.

MC-LR disrupts dopamine synthesis in the substantia nigra of midbrain by enhancing the chaperone-mediated autophagy pathway through direct binding to ERK2

Microcystins are environmental toxins produced by freshwater cyanobacteria. Microcystin-LR (MC-LR) is one of the most abundant and harmful isomers. MC-LR poses a serious threat to human health. MC-LR could penetrate the blood-brain barrier of mice and accumulate in the substantia nigra (SN) of the midbrain, leading to a reduction in dopamine levels and Parkinson's disease (PD)-like motor dysfunction in mice. The reduction in dopamine levels is a key factor contributing to movement disorders in humans with PD. Dopamine is synthesized in the dopaminergic neurons of the SN by the actions of tyrosine hydroxylase (TH) and dihydroxyphenylalanine decarboxylase (DDC). In this study, we found that MC-LR could enter dopaminergic neurons in the SN and directly bound to extracellular signal-regulated kinase 2 (ERK2), enhancing ERK2 stability. ERK2 further enhanced the transcriptional activity of Heat Shock Protein Family A Member 8 (HSPA8) and promoted the expression of Heat shock cognate 71 kDa protein (HSC70), which in turn amplified the chaperone-mediated autophagy (CMA) pathway and accelerated the degradation of TH and DDC. This affected the dopamine synthesis process, resulting in a significant reduction in dopamine levels. The study is the first to reveal that ERK2 was a direct target of MC-LR, and further enhanced CMA affecting dopamine synthesis, which has important theoretical and practical significance for environmental safety management.

Nicotinamide Alleviates Synergistic Impairment of Intestinal Barrier Caused by MC-LR and NaNO2 Coexposure.

Microcystin-LR (MC-LR) and nitrites from the environment and daily life can be ingested and absorbed by humans via the digestive tract. However, their combined effects on intestinal health remain unclear. Here, the combined impact of MC-LR and sodium nitrite (NaNO2) on the intestines of mice was investigated under actual human exposure conditions. After mice were exposed to MC-LR (10, 100 μg/L) and NaNO2 (30, 300 mg/L) individual and in combination for 6 months, it was found that MC-LR and NaNO2 synergistically decreased intestinal permeability and disrupted intestinal physical, chemical, immune, and microbial barriers. In the coexposure groups, the synergistic impairment to the intestinal barrier was noted with increasing concentrations of MC-LR or NaNO2, but this adverse effect was alleviated by nicotinamide supplementation. This study underscores the potential risks of simultaneous ingestion of MC-LR and nitrite on intestinal health. The protective role of nicotinamide suggests avenues for therapeutic intervention against environmental toxin-induced intestinal impairment.

Nanozyme and bifunctional nanobody-based colorimetric-SERS dual-mode Immunosensor for microcystin-LR detection

Microcystin-LR (MC-LR), a potent cyanotoxin in freshwater, poses a risk of severe liver damage and other health issues, making its detection vital. However, the detection capabilities of conventional antibodies are constrained, which limited their use in immunoassays. In this work, we designed a new bifunctional nanobody, named A2.3-SBP (comprised of nanobody and streptavidin binding peptide), capable of binding with MC-LR and streptavidin. Based on A2.3-SBP and Fe3O4@Au-Pt nanozyme, we introduced an enzyme-free immunosensor that operated in microplate with colorimetric and surface-enhanced Raman scattering (SERS) detection modes. The dual-mode assay showed color changes and SERS intensity directly correlating to MC-LR concentrations with a range from 1.0 to 500 ng/mL and a limit of detection of 0.26 and 0.032 ng/mL, respectively. This strategy eliminated the need for complex enzymatic reactions and realized dual-signal detection of MC-LR in 96 water samples (0.03 μg/kg) within 30 min, suggesting its potential in drinking water detection.

Detection and monitoring of MC-LR and MC-RR in the artifical irrigation ponds at Oltu district

Although it is defining as natural organic pollutant, surface water resources which are frequently exposed to Harmful Algae Blooms (HABs) due to the increasing nutrient loading in recent years, the increase in temperature caused by climate change and the increase in surface run-off caused by extreme rainfall as a result of the risk of the increasing concentrations of algal toxins into drinking water. Although HABs have caused the problem of eutrophication in surface waters especially at hot seasons in the past decades due to the water pollution, increasing surface water temperatures with climate change cause this problem to extended periods out of season and to be permanent for the year. Therefore, studies including the detection and monitoring of algal toxins are gaining importance in order to observe HAB events at their source. As global temperature increases, HAB events have spread to regions that have even cold climates. Consequently, Microcystin-LR (MC-LR) and Microcystin-RR (MC-RR), which are the main indicators of HAB events in surface waters were aimed to detect and monitor at the artificial ponds designed for agriculture and animal husbandry purposes in Oltu District of Erzurum Province which has cold climate, for the first time in this study.Microcystins (MCs) concentrations were measured in the samples taken from ponds in four seasons for one year, by LC-MS/MS and; water temperature and pH values were also determined simultaneously. The relationship between the MC-LR and MC-RR distributions and, the pH and temperature were calculated by Pearson Correlation Coefficient (r).

Effects of cyanotoxins on nitrogen transformation in aquaculture systems with microplastics coexposure: Adsorption behavior, bacterial communities and functional genes

Microcystin-LR (MC-LR) and microplastics (MPs) have attracted increasing attention as important new pollutants in freshwater fishery environments. However, there are few reports on the effects of long-term combined MC-LR and MPs pollution on nitrogen transformation and microbial communities in aquaculture ponds, and the resulting risks have yet to be determined. Therefore, in this study, traditional refractory MPs (polystyrene, PS), biodegradable MPs (polylactic acid, PLA) and MC-LR, which are common in freshwater fishery environments in China, were selected as pollutants to construct a microcosm that simulates freshwater aquaculture ponds. MC-LR coexposure to PS and PLA was tested to reveal the effects of these pollutants on nitrogen transformation and microbial communities in aquaculture ponds, as well as to elucidate the potential risks posed by traditional refractory MPs and biodegradable MPs to freshwater aquaculture ecosystems. The results revealed that the MPs had a relatively high adsorption rate for MC-LR and that PS presented a relatively high adsorption capacity, whereas PLA presented a relatively high desorption capacity. Single or combined MPs and MC-LR pollution disrupted the normal nitrogen cycle in the aquaculture system, causing an overall loss of nitrogen in the water, and denitrification and nitrogen fixation in the water were inhibited to a certain extent through the inhibition of nitrogen cycle-related functional genes, with the PS + MC-LR group having the greatest inhibitory effect. In addition, compared with single-pollutant exposure, combined exposure to MC-LR and MPs had a greater effect on the microbial community composition. Analysis of the integrated biomarker response (IBR) index revealed that the risk of combined exposure to MC-LR and PS was greater than that of single exposure, so this phenomenon merits further attention.

Multivalent bifunctional nanobody to enhance the sensitivity of direct competitive chemiluminescence immunoassay for the detection of microcystin LR in lake water

Microcystin-LR (MC-LR), a toxic cyanobacterial toxin in freshwater, poses significant health and ecological risks due to its ability to induce cell apoptosis and liver damage. Sensitive detection of MC-LR is crucial for public health and water safety. In this work, we engineered a multivalent bifunctional nanobody (A2.3-C4-SBP) by fusing the anti-MC-LR nanobody gene (A2.3) with self-assembling peptides (C4) and a streptavidin-binding peptide (SBP). A2.3-C4-SBP was directionally immobilized on the ELISA microplate via streptavidin-mediated to develop a multivalent bifunctional nanobody-based chemiluminescent immunoassay (MBN-CLIA) for MC-LR detection in lake water. The IC50 of the A2.3-C4-SBP heptamer based CLIA was 5.80 ng/mL, and the LOD (IC10) was 0.33 ng/mL, which were 9.51-fold and 1.82-fold lower, respectively, than those of the A2.3-SBP monomer based CLIA. Additionally, the IC50 and LOD were 1.26-fold and 1.82-fold lower, respectively, than those of the A2.3-C4-SBP heptamer without streptavidin-mediated directional immobilization. In summary, this work developed a sensitive, rapid and simple immunoassay for the detection of MC-LR in lake water based on multivalent bifunctional nanobodies. Furthermore, the proposed combined strategy of nanobody multimerization and directed immobilization is simple to operate and has great potential to improve the sensitivity and signal amplification of various immunoassays.

Toxicological and mechanistic insights into organic contaminants released from on-line membrane cleaning during ultrafiltration of algal-containing waters

Eutrophication has significantly challenged the treatment of algae-contaminated water. Ultrafiltration has become an essential method for water purification, though frequent on-line chemical cleaning is necessary to maintain membrane permeability. This study aims to systematically investigate the impact of various chemical cleaning agents on the release of dissolved organic matters and toxic by-products, particularly from algal cells. Through a series of controlled experiments, Microcystis aeruginosa cells were exposed to different cleaning agents (HCl, NaOH, NaClO), and the resulting DOM and by-products were characterized. Special attention was paid to the release of intracellular organic matter (IOM) and extracellular organic matter (EOM). Results revealed that NaClO significantly oxidized IOM, leading to the formation of humic-like substances and halogenated organic compounds (TOX), including 15 types of halogenated by-products detected by UPLC/ESI-tqMS. Furthermore, the release of toxic microcystin LR (MC-LR) was traced primarily to IOM. The removability of these contaminants by UF and reverse osmosis (RO) membranes was analyzed, revealing that over 50% of the toxic by-products passed through UF membranes, and 10% still penetrated RO membranes, raising significant concerns for downstream water quality and drinking water safety.

Temperature dependent sensitivity of the harpacticoid copepod Nitokra spinipes to marine algal toxins

Harmful algal blooms (HABs) – proliferated algae densities, often producing toxins – have increasingly been found in ocean and coastal areas. Recent studies show that rising temperatures contribute to HAB occurrence, but the broader influence of climate change on these outbreaks is less quantified. Of particular concern is the limited research on HAB toxin effects under varying temperatures, especially regarding primary consumers such as copepods, a crucial component of aquatic ecosystems. Therefore, we examined the impact of marine toxins on the harpacticoid copepod Nitokra spinipes, a model organism for marine ecotoxicology, in the context of climate change. We evaluated the toxicity of four purified, commonly occurring algal toxins, at three different temperatures in the laboratory. First, adult females were exposed to a concentration series of toxins at 15, 20, and 25 °C for 48 hours. EC50 values of domoic acid ranged from 8.79 ± 1.93 μg L-1 to 25.97 ± 11.96 μg L-1. Nauplii, aged 48 to 72 hours, were exposed at 18, 20 and 22 °C for the same duration. Less sensitive compared to adults, the EC50 of domoic acid in this case varied from 57.26 ± 6.82 μg L-1 to 97.24 ± 6.45 μg L-1. Both results indicated a temperature-dependent EC50. For the chronic toxicity tests, larval development ratio (LDR), brood size and inter-brood time of domoic acid (DA), yessotoxin (YTX), saxitoxin (STX), and microcystin-LR (MC-LR) were examined at 18, 20 and 22 °C. We observed that with increasing temperatures, LDR increased, whereas brood size significantly decreased as DA, YTX or STX concentrations rose. No interaction between temperature and algal toxins was found but a temperature dependent sensitivity of copepods towards DA, YTX and STX was revealed. Our research provides insights into the effects of long-term exposure to algal toxins on marine copepods and the potential impacts of climate warming.

In-situ photoelectrochemical surface-enhanced Raman scattering based on Au@Ag/WO3 hollow microsphere for dual-mode sensing of microcystin-LR

Developing an accurate assay for early warning of microcystin-LR (MC-LR) is of great importance for environmental protection and agricultural production. Herein, this paper reported an in-situ photoelectrochemical surface-enhanced Raman scattering (PEC-SERS) strategy for dual-mode detection of MC-LR. The Au@Ag core-cell nanoparticles loaded hollow WO3 microsphere (Au@Ag/H-WO3) acted as in-situ PEC-SERS substrate to take advantage of the synergy between electromagnetic and chemical enhancement, while methylene blue (MB) was chosen as a bifunctional probe to produce photocurrent and SERS signal. For this strategy, double signals from MB were simultaneously induced by a 532 nm laser that the SERS signal and photocurrent offered a 57.9-fold and a 4.7-fold amplification, respectively, in the presence of Au@Ag/H-WO3. For analysis, the binding of MC-LR to aptamer led to the stripping of MB from the substrate and further decreased signals. Such a strategy offered linear ranges of 0.3–50 ng/mL in PEC mode while 1–100 ng/mL in SERS mode for MC-LR detection with high accuracy and applicability for real sample analysis. This in-situ PEC-SERS strategy offered an efficient way to monitor hazardous materials in the environment and agriculture.

Analysis of Total Microcystins using LC-MS/MS: Method Improvements and Sample Applications

Microcystin variants (MCs), including microcystin-LR (MC-LR) and related variants, are produced by cyanobacteria and are regulated due to their potential health risks. Current methods for MC analysis predominantly employ LC-MS/MS, limited by the availability of reference materials necessary for quantification. As an alternative method for total MC quantification, the analysis of 2-methyl-3-methoxy-4-phenylbutyric acid (MMPB), formed by oxidation of the common ADDA structure in MCs, offers economic and practical advantages by avoiding the need for multiple MC reference materials. This method allows total MC quantification across various matrices, independent of specific MC variants. In this study, we evaluated the utility of MMPB-d3 as a surrogate to assess recovery rates throughout the processes critical for MMPB quantification. Comparative analysis with 4-phenylbutyric acid (4-PB) highlighted the stability of MMPB-d3 under oxidative conditions, which is critical for its application as a surrogate or internal standard. The oxidation process was optimized to achieve consistent recovery rates, averaging 101%, ensuring reliable conversion of MCs to MMPB for subsequent analysis. The limit of quantification (LOQ) has been improved due to the large volume injection of up to 0.1 µg/L. Comparison of MMPB concentrations from field samples with conventional LC-MS/MS results showed a significant correlation (r = 0.80, p < 0.005), but with variations in the absolute concentrations. Calculations using a formulation model with MMPB concentrations allowed us to estimate total MC levels, demonstrating the potential of the proposed method to complement existing target measurement techniques.

Relationships between extracellular microcystin LR and fecal bacterial indicators in a shallow urban lake: the Ypacarai Lake (Paraguay)

Relationships between extracellular microcystin LR and fecal bacterial indicators in a shallow urban lake: the Ypacarai Lake (Paraguay)

Astaxanthin Alleviates Hepatic Lipid Metabolic Dysregulation Induced by Microcystin-LR.

Microcystin-LR (MC-LR), frequently generated by cyanobacteria, has been demonstrated to raise the likelihood of liver disease. Few previous studies have explored the potential antagonist against MC-LR. Astaxanthin (ASX) has been shown to possess various beneficial effects in regulating lipid metabolism in the liver. However, whether ASX could alleviate MC-LR-induced hepatic lipid metabolic dysregulation is as yet unclear. In this work, the important roles and mechanisms of ASX in countering MC-LR-induced liver damage and lipid metabolic dysregulation were explored for the first time. The findings revealed that ASX not only prevented weight loss but also enhanced liver health after MC-LR exposure. Moreover, ASX effectively decreased triglyceride, total cholesterol, aspartate transaminase, and alanine aminotransferase contents in mice that were elevated by MC-LR. Histological observation showed that ASX significantly alleviated lipid accumulation and inflammation induced by MC-LR. Mechanically, ASX could significantly diminish the expression of genes responsible for lipid generation (Srebp-1c, Fasn, Cd36, Scd1, Dgat1, and Pparg), which probably reduced lipid accumulation induced by MC-LR. Analogously, MC-LR increased intracellular lipid deposition in THLE-3 cells, while ASX decreased these symptoms by down-regulating the expression of key genes in the lipid synthesis pathway. Our results implied that ASX played a crucial part in lipid synthesis and effectively alleviated MC-LR-induced lipid metabolism dysregulation. ASX might be developed as a novel protectant against hepatic impairment and lipid metabolic dysregulation associated with MC-LR. This study offers new insights for further management of MC-LR-related metabolic diseases.

Assessing the response lettuce and arugula to MC-LR-contaminated water irrigation: photosynthetic changes and antioxidant defense.

Irrigation of crops with cyanotoxin-contaminated water poses a significant risk to human health. The direct phytotoxic effects of microcystin-LR (MC-LR), one of the most toxic and prevalent microcystin variants in water bodies, can induce physiological stress and hinder crop development and production. This study investigated the impact of environmentally relevant concentrations of MC-LR (1 to 10µg L-1) on photosynthetic parameters and antioxidant response of lettuce (Lactuca sativa L.) and arugula (Eruca sativa L.) following irrigation with contaminated water. During the 15-day experiment, lettuce and arugula were exposed to various concentrations of MC-LR, and their photosynthetic rates, stomatal conductance, leaf tissue transpiration, and intercellular CO2 concentrations were measured using an infrared gas analyzer. These results suggest that the influence of MC-LR on gas exchange in crops is concentration-dependent, with notable disruptions during exposure and recovery tendency during detoxification. Antioxidant response analysis revealed that glutathione S-transferase (GST) and superoxide dismutase (SOD) activities were upregulated during the exposure phase in the presence of MC-LR. However, GST activity decreased during the detoxification phase in both crops, although the effects of the toxin at 10µg L-1 were still evident in arugula. The internal H2O2 concentration in the crops increased after exposure to MC-LR, showing a time- and concentration-dependent pattern, with an increase during the exposure phase (days 1-7) and a decrease during the detoxification phase (days 8-15). Irrigation of lettuce and arugula with MC-LR-contaminated water affected various aspects of the photosynthetic apparatus and antioxidant responses, which could influence the general health and productivity of exposed crops at environmentally relevant microcystin concentrations. Furthermore, investigation of additional vegetable species and long-term MC-LR exposure can be crucial for understanding the extent of contamination risk, detoxification mechanisms, and other parameters affecting these crops.

Nephrotoxicity of Cylindrospermopsin (CYN) and Microcystin-LR (MC-LR) on Mammalian Kidney: Wistar Rat as a Model Assessment

Naturally derived cyanotoxins, cylindrospermopsin (CYN), and microcystin-LR (MC-LR) have shown hepatotoxic and nephrotoxic effects in several studies. The present study aimed to determine the possible nephrotoxicity of MC-LR and CYN on mammalian kidneys using male Wistar rats as an animal model. Potential nephrotoxicity was evaluated at different doses of CYN (0.175 μg.kg-1, 0.140 μg.kg-1, 0.105 μg.kg-1) and MC-LR (0.105 μg.kg-1, 0.070 μg.kg-1, 0.035 μg.kg-1) was observed. Water samples from dug wells contaminated with CYN (0.161 μg.kg-1) and MC-LR (0.091 μg.kg-1) from the Padaviya area in Anuradhapura, Sri Lanka were used as environmental samples. The control groups were treated with distilled water. The exposure time of rats to the toxin was 90 days. Evaluation of urinary creatinine, serum creatinine, and Kidney Injury Molecule-1 (KIM-1) were estimated using standard protocols. A significant increase in serum creatinine levels was observed in all CYN and MC-LR treated groups (p<0.05) after 7 and 42 days of exposure, respectively, compared to control. It was found a decrease of urine creatinine when rats were treated with different concentrations of CYN and MC-LR (p<0.05) after 7 days compared to the control. The highest KIM-1 concentrations were recorded at 0.175 μg.kg-1 of CYN and 0.105 μg.kg-1 of MC-LR. The concentrations of KIM-1 in the control groups for CYN-treated and MC-LR-treated were not detected. Luminal protein, nuclear pyknosis, mild tubular epithelial swelling, vascular congestion, and interstitial inflammation in CYN and MC-LR treated groups were common. No predominant changes were observed in the control groups treated with CYN and MC-LR. The results of the present study confirm that the consumption of CYN and MC-LR-contaminated water may lead to kidney injury in Wistar rats.

Effects of Harmful Algal Blooms on Amphibians and Reptiles are Under-Reported and Under-Represented.

Harmful algal blooms (HABs) are a persistent and increasing problem globally, yet we still have limited knowledge about how they affect wildlife. Although semi-aquatic and aquatic amphibians and reptiles have experienced large declines and occupy environments where HABs are increasingly problematic, their vulnerability to HABs remains unclear. To inform monitoring, management, and future research, we conducted a literature review, synthesized the studies, and report on the mortality events describing effects of cyanotoxins from HABs on freshwater herpetofauna. Our review identified 37 unique studies and 71 endpoints (no-observed-effect and lowest-observed-effect concentrations) involving 11 amphibian and 3 reptile species worldwide. Responses varied widely among studies, species, and exposure concentrations used in experiments. Concentrations causing lethal and sublethal effects in laboratory experiments were generally 1 to 100 µg/L, which contains the mean value of reported HAB events but is 70 times less than the maximum cyanotoxin concentrations reported in the environment. However, one species of amphibian was tolerant to concentrations of 10,000 µg/L, demonstrating potentially immense differences in sensitivities. Most studies focused on microcystin-LR (MC-LR), which can increase systemic inflammation and harm the digestive system, reproductive organs, liver, kidneys, and development. The few studies on other cyanotoxins illustrated that effects resembled those of MC-LR at similar concentrations, but more research is needed to describe effects of other cyanotoxins and mixtures of cyanotoxins that commonly occur in the environment. All experimental studies were on larval and adult amphibians; there were no such studies on reptiles. Experimental work with reptiles and adult amphibians is needed to clarify thresholds of tolerance. Only nine mortality events were reported, mostly for reptiles. Given that amphibians likely decay faster than reptiles, which have tissues that resist decomposition, mass amphibian mortality events from HABs have likely been under-reported. We propose that future efforts should be focused on seven major areas, to enhance our understanding of effects and monitoring of HABs on herpetofauna that fill important roles in freshwater and terrestrial environments. Environ Toxicol Chem 2024;43:1936-1949. Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Microcystin-LR Regulates Interaction between Tumor Cells and Macrophages via the IRE1α/XBP1 Signaling Pathway to Promote the Progression of Colorectal Cancer.

Microcystin-LR (MC-LR), a cyanobacterial toxin, is a potent carcinogen implicated in colorectal cancer (CRC) progression. However, its impact on the tumor microenvironment (TME) during CRC development remains poorly understood. This study investigates the interaction between tumor cells and macrophages mediated by MC-LR within the TME and its influence on CRC progression. CRC mice exposed to MC-LR demonstrated a significant transformation from adenoma to adenocarcinoma. The infiltration of macrophages increased, and the IRE1α/XBP1 pathway was activated in CRC cells after MC-LR exposure, influencing macrophage M2 polarization under co-culture conditions. Additionally, hexokinase 2 (HK2), a downstream target of the IRE1α/XBP1 pathway, was identified, regulating glycolysis and lactate production. The MC-LR-induced IRE1α/XBP1/HK2 axis enhanced lactate production in CRC cells, promoting M2 macrophage polarization. Furthermore, co-culturing MC-LR-exposed CRC cells with macrophages, along with the IRE1α/XBP1 pathway inhibitor 4μ8C and the hexokinase inhibitor 2-DG, suppressed M2 macrophage-induced CRC cell migration, clonogenicity, and M2 macrophage polarization. This study elucidates the mechanism by which MC-LR-mediated interactions through the IRE1α/XBP1 pathway promote CRC progression, highlighting potential therapeutic targets.