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To date there are only pirfenidone (PFD) and nintedanib to be given conditional recommendation in idiopathic pulmonary fibrosis (IPF) therapies with slowing disease progression, but neither has prospectively shown a reduced mortality. It is one of the urgent topics to find effective drugs for pulmonary fibrosis in medicine. Previous studies have demonstrated that microcystin-RR (MC-RR) effectively alleviates bleomycin-induced pulmonary fibrosis, but the mechanism has not been fully elucidated yet. We further conducted a comparison of therapeutic effect on the model animals of pulmonary fibrosis between MC-RR and PFD with histopathology and the expression of the molecular markers involved in differentiation, proliferation and metabolism of myofibroblasts, a major effector cell of tissue fibrosis. The levels of the enzyme molecules for maintaining the stability of interstitial structure were also evaluated. Our results showed that MC-RR and PFD effectively alleviated pulmonary fibrosis in model mice with a decreased signaling and marker molecules associated with myofibroblast differentiation and lung fibrotic lesion. In the meantime, both MC-RR and PFD treatment are beneficial to restore molecular dynamics of interstitial tissue and maintain the stability of interstitial architecture. Unexpectedly, MC-RR, rather than PFD, showed a significant effect on inhibiting PKM2-HIF-1α signaling and reducing the level of p-STAT3. Additionally, MC-RR showed a better inhibition effect on FGFR1 expression. Given that PKM2-HIF-1α and activated STAT3 molecular present a critical role in promoting the proliferation of myofibroblasts, MC-RR as a new strategy for IPF treatment has potential advantage over PFD. [Display omitted] • Low toxicity microcystin-RR effectively alleviates pulmonary fibrosis as pirfenidone. • The medicinal application of microcystin-RR in pulmonary fibrosis could have better safety. • Microcystin-RR suppresses pyruvate kinase M2 signaling but pirfenidone does not. • Microcystin-RR impedes markedly the augment of fibroblast growth factor receptor 1. [ABSTRACT FROM AUTHOR]

Coupling different energy harvesting technologies to obtain an excellent output signal is essential for the development of high-performance self-powered electrochemical sensors. Herein, a novel hydrovoltaic-photothermal coupling self-powered electrochemical aptasensing platform was designed for sensitive detection of microcystin (MC-RR) with a digital multimeter as a direct visual readout strategy. The straightforward ultrasonic method was employed to synthesize polyaniline (PANI) and bismuth oxybromide (BiOBr) nanosheets, which were then integrated as active components in a hydrovoltaic device. The unique layer structure of two-dimensional (2D) nanomaterials BiOBr can create flexible interlayer spaces to accommodate various ions and water molecules, which was beneficial to construct evaporation-driven channels. Meanwhile, the exceptional photothermal characteristics of polyaniline could accelerate the water evaporation rate, consequently boosting the migration speed of charge carriers and increasing output signal. Moreover, a digital multimeter was connected to the constructed sensor for real-time displaying the output signal. With the assistance of aptamer, a novel self-powered electrochemical aptasensing platform was constructed for sensitive detection of MC-RR. Under optimum conditions, the output signal of the hydrovoltaic-photothermal coupling cell was linearly related to the logarithm of MC-RR concentration in the range of 1 fM to 1 nM with a detection limit of 0.31 fM (S/N = 3). Furthermore, this sensor also exhibited many advantages such as high selectivity, good repeatability and portability. Such novel strategy not only offers a completely new general approach to construct high-performance self-powered devices for the detection of MC-RR, but also provides a new strategy for advancing the miniaturization and field application of self-powered electrochemical sensors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microcystins (MC)-RR is a significant analogue of MC-LR, which has been identified as a hepatotoxin capable of influencing lipid metabolism and promoting the progression of liver-related metabolic diseases. However, the toxicity and biological function of MC-RR are still not well understood. In this study, the toxic effects and its role in lipid metabolism of MC-RR were investigated in hepatoblastoma cells (HepG2cells). The results demonstrated that MC-RR dose-dependently reduced cell viability and induced apoptosis. Additionally, even at low concentrations, MC-RR promoted lipid accumulation through up-regulating levels of triglyceride, total cholesterol, phosphatidylcholines and phosphatidylethaolamine in HepG2 cells, with no impact on cell viability. Proteomics and transcriptomics analysis further revealed significant alterations in the protein and gene expression profiles in HepG2 cells treated with MC-RR. Bioinformatic analysis, along with subsequent validation, indicated the upregulation of CD36 and activation of the AMPK and PI3K/AKT/mTOR in response to MC-RR exposure. Finally, knockdown of CD36 markedly ameliorated MC-RR-induced lipid accumulation in HepG2 cells. These findings collectively suggest that MC-RR promotes lipid accumulation in HepG2 cells through CD36-mediated signal pathway and fatty acid uptake. Our findings provide new insights into the hepatotoxic mechanism of MC-RR. MC-RR exposure promotes up-regulation of CD36 and activates the AMP-activated protein kinase (AMPK) and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, resulting in a significant augmentation of cellular triglycerides (TG), total cholesterol (T-CHO), phosphatidylethanolamine (PE), and phosphatidylcholine (PC), thus driving the observed lipid accumulation. [Display omitted] • Low concentration of MC-RR retains cell viability but promotes lipid accumulation. • MC-RR leads to augmentation of triglycerides, total cholesterol, phosphatidylethanolamine, and phosphatidylcholine. • MC-RR exposure induces significant up-regulation of CD36. • MC-RR activates AMPK and PI3K/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pulmonary disease characterized with radiographically evident pulmonary infiltrates and extracellular matrix deposition with limited treatment options. We previously described that microcystin-LR (MC-LR) reduces transforming growth factor (TGF)-β1/Smad signaling and ameliorates pulmonary fibrosis in bleomycin (BLM)-induced rat models. In the present study, we further demonstrate that microcystin-RR (MC-RR), an MC congener with lower toxicity than MC-LR, exerted an anti-fibrotic effect on BLM-induced pulmonary fibrosis rodent models and compared it with MC-LR. Our data show that MC-RR treatment attenuated BLM-associated pulmonary inflammation and collagen deposition in both therapeutic and preventive models. MC-RR reduced the expression of fibrotic markers, including vimentin, α-smooth muscle actin, collagen 1α1, and fibronectin, in rat pulmonary tissues. Furthermore, the core features of BLM-induced pulmonary fibrotic lesions were better alleviated by MC-RR than by MC-LR. MC-RR treatment substantially decreased the number of pulmonary M2 macrophages. In vitro, MC-RR attenuated the epithelial-mesenchymal transition and fibroblast-myofibroblast transition triggered by M2 macrophages. Therefore, we highlight MC-RR as a promising molecule for developing therapeutic and prophylactic strategies against IPF, a refractory lung disease.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pulmonary disease characterized with radiographically evident pulmonary infiltrates and extracellular matrix deposition with limited treatment options. We previously described that microcystin-LR (MC-LR) reduces transforming growth factor (TGF)-β1/Smad signaling and ameliorates pulmonary fibrosis in bleomycin (BLM)-induced rat models. In the present study, we further demonstrate that microcystin-RR (MC-RR), an MC congener with lower toxicity than MC-LR, exerted an anti-fibrotic effect on BLM-induced pulmonary fibrosis rodent models and compared it with MC-LR. Our data show that MC-RR treatment attenuated BLM-associated pulmonary inflammation and collagen deposition in both therapeutic and preventive models. MC-RR reduced the expression of fibrotic markers, including vimentin, α-smooth muscle actin, collagen 1α1, and fibronectin, in rat pulmonary tissues. Furthermore, the core features of BLM-induced pulmonary fibrotic lesions were better alleviated by MC-RR than by MC-LR. MC-RR treatment substantially decreased the number of pulmonary M2 macrophages. In vitro , MC-RR attenuated the epithelial-mesenchymal transition and fibroblast-myofibroblast transition triggered by M2 macrophages. Therefore, we highlight MC-RR as a promising molecule for developing therapeutic and prophylactic strategies against IPF, a refractory lung disease. [ABSTRACT FROM AUTHOR]

The canonical mode of action (MOA) of microcystins (MC) is the inhibition of protein phosphatases, but complete characterization of toxicity pathways is lacking. The existence of over 200 MC congeners complicates risk estimates worldwide. This work employed RNA-seq to provide an unbiased and comprehensive characterization of cellular targets and impacted cellular processes of hepatocytes exposed to either MC-LR or MC-RR congeners. The human hepatocyte cell line, HepaRG, was treated with three concentrations of MC-LR or -RR for 2 h. Significant reduction in cell survival was observed in LR1000 and LR100 treatments whereas no acute toxicity was observed in any MR-RR treatment. RNA-seq was performed on all treatments of MC-LR and -RR. Differentially expressed genes and pathways associated with oxidative and endoplasmic reticulum (ER) stress, and the unfolded protein response (UPR) were highly enriched by both congeners as were inflammatory pathways. Genes associated with both apoptotic and inflammatory pathways were enriched in LR1000. We present a model of MC toxicity that immediately causes oxidative stress and leads to ER stress and the activation of the UPR. Differential activation of the three arms of the UPR and the kinetics of JNK activation ultimately determine whether cell survival or apoptosis is favored. Extracellular exosomes were enrichment of by both congeners, suggesting a previously unidentified mechanism for MC-dependent extracellular signaling. The complement system was enriched only in MC-RR treatments, suggesting congener-specific differences in cellular effects. This study provided an unbiased snapshot of the early systemic hepatocyte response to MC-LR and MC-RR congeners and may explain differences in toxicity among MC congeners.

A novel biological material named activated carbon fibers-sodium alginate@Sphingopyxis sp. YF1 (ACF-SA@YF1) was synthesized for microcystin-RR (MC-RR) and nutrient pollutant degradation in eutrophic water. The synthesized biomaterial was characterized by scanning electron microscopy (SEM). Box-Behnken design and response surface methodology (RSM) were utilized for the optimization of conditions during the MC-RR degradation. The degradation of MC-RR and nutrient pollutants was dynamically detected. The results revealed that the optimal conditions were temperature 32.51 °C, pH 6.860, and inoculum 14.97%. The removal efficiency of MC-RR, nitrogen, phosphorus, and chemical oxygen demand were 0.76 μg/mL/h, 32.45%, 94.57%, and 64.07%, respectively. In addition, ACF-SA@YF1 also performed satisfactory cyclic stability, while the MC-RR removal efficiency was 70.38% after seven cycles and 78.54% of initial activity after 20 days of storage. Therefore, it is reasonable to believe that ACF-SA@YF1 is an effective material which has a great prospect in removing MC-RR and nutrients from freshwater ecosystems. [ABSTRACT FROM AUTHOR]

Microcystins (MCs) are toxins produced by several cyanobacterial species found worldwide. While MCs have a common structure, the variation of two amino acids in their structure affects their toxicity. As toxicodynamics are very similar between the MC variants, their differential toxicity could rather be explained by toxicokinetic parameters. Microcystin-RR (MC-RR) is the second most abundant congener and induces toxicity through oral exposure. As intestinal permeability is a key parameter of oral toxicokinetics, the apparent permeability of MC-RR across a differentiated intestinal Caco-2 cell monolayer was investigated. We observed a rapid and large decrease of MC-RR levels in the donor compartment. However, irrespective of the loaded concentration and exposure time, the permeabilities were very low from apical to basolateral compartments (from 4 to 15 × 10−8 cm·s−1) and from basolateral to apical compartments (from 2 to 37 × 10−8 cm·s−1). Our results suggested that MC-RR would be poorly absorbed orally. As similar low permeability was reported for the most abundant congener microcystin-LR, and this variant presented a greater acute oral toxicity than MC-RR, we concluded that the intestinal permeability was probably not involved in the differential toxicity between them, in contrast to the hepatic uptake and metabolism.

Toxic cyanobacteria (TCB) are well-known worldwide for their adverse impacts on humans. Species compositions and seasonal variations of TCB in reservoirs depend on interactions between physical and chemical factors. This study was conducted to evaluate the water quality in the Aha Reservoir, Southwest China, focusing on cyanobacteria and cyanotoxins. Water samples were collected weekly or biweekly from May to September of 2015 and used to delineate temporal variations in density and distribution of toxic cyanobacteria and cyanotoxins in the reservoir. Toxic cyanobacteria identified consisted of Aphanizomenon flos-aquae, Pseudanabaena limnetica, Cylindrospermopsis sp., and Microcystis sp., with Aphanizomenon flos-aquae and Pseudanabaena limnetica being the most common and significant toxic genera. The total biomass of cyanobacteria was 17.0 mg/L. Identification and quantification of microcystin variants were conducted by high performance liquid chromatography (HPLC) using a system equipped with a photodiode array detector. Microcystin levels were between 0–3.0 μg/L, MC-RR was around 0–3.0 μg/L and MC-LR was approximately 0–0.9 μg/L. Overall, the results of this study indicate that the investigated reservoirs should be monitored regularly to minimize potential health risks to the human population. [ABSTRACT FROM AUTHOR]

Information on the catalytic role of mlrA gene-encoded enzyme (MlrA) in microcystin-RR (MC-RR) biodegradation was limited. This study succeeded in expressing mlrA homolog of Novosphingobium sp. THN1 in heterologous host for the first time, by constructing a recombinant bacterium. Mass spectrometric analysis showed that the recombinant MlrA hydrolyzed MC-RR into linear intermediate product by cleaving the peptide bond between Adda and arginine residue, greatly detoxifying MC-RR. This finding clearly manifested that the MlrA homolog of THN1 strain possesses its original catalytic function, and ring-opening constituted the first step in MC-RR biodegradation pathway of THN1 strain. Moreover, MC-RR degradation by intact recombinant cells and cell-free crude enzyme (CE) from recombinant was compared. Results exhibited that intact recombinant was able to degrade 20 μg mL −1 MC-RR more quickly than CE, with the maximum rate of 9.22 μg mL −1 h −1 in the first 8 h. Thus, this study provided new insights on the catalytic activity and roles of MlrA originated from THN1 strain in MC-RR biodegradation process, which lay a foundation for efficiently removing and detoxifying MC-RR, and exploring downstream steps in MC-RR biodegradation pathway of THN1 strain. [ABSTRACT FROM AUTHOR]

Microcystins (MCs) are a group of monocyclic heptapeptide toxins that have been shown to act as potent hepatotoxins. However, the observed symptoms of water metabolism disruption induced by microcystin-RR (MC-RR) or MCs have rarely been reported, and a relatively clear mechanism has not been identified. In the present study, male mice were divided into 4 groups (A: 140 μg/kg, B: 70 μg/kg, C: 35 μg/kg, and D: 0 μg/kg) and administered MC-RR daily for a month. On day 8 of treatment, an increase in water intake and urine output was observed in the high-dose group compared with the control, and the symptoms worsened with the repeated administration of the toxin until day 30. In addition, the urine specific gravity decreased and serum enzymes that can reflect hepatic damage increased in the high-dose group compared with the control ( P < 0.05 ). The mRNA level of angiotensinogen (AGT) in hepatocytes was upregulated to approximately 150% of the control ( P < 0.05 ), and the serum renin-angiotensin system (RAS) was activated in the high-dose group; however, signs of renal injury were not observed throughout the experiment. After the toxin treatment was completed, the high levels of the RAS and vasopressin in group A returned to normal levels within 1 week. As expected, the symptoms of polyuria and polydipsia also disappeared. Therefore, we propose that water metabolism dysfunction occurs via RAS activation caused by liver damage because the increased serum RAS levels in the experiment were consistent with the increased urine output and water intake in the mice during the observation period. In addition, we found for the first time that a RAS blocker could alleviate the observed polyuria and polydipsia and inactivate the high level of the RAS induced by MC-RR in a dose-dependent manner, which further supported our hypothesis. [ABSTRACT FROM AUTHOR]

Microcystins produced during the outbreak of cyanobacteria are a serious threat to human beings and the ecological environment, so it's important to remove microcystins from water. In this study, the magnetic metal-organic framework (MOFs) Fe 3 O 4 @ZIF-8 was prepared to adsorb microcystins. The characterization of the structure, morphology and properties of the material showed that the material had high specific surface area, great paramagnetism and obvious core-shell structure. At the same time, the effects of pH, contact time, initial concentration of microcystin-RR, temperature, coexisting ions, real water and reusability were investigated and the kinetic models and isotherm models were established. The results showed that the adsorption processes were well described by the pseudo-second-order kinetic model and Freundlich isotherm model, indicating that the adsorption process was chemical heterogeneous multi-layer adsorption process. In addition, when pH = 6.0 and temperature was 298 K, the theoretical maximum adsorption capacity of Fe 3 O 4 @ZIF-8 was calculated to be 6.055 mg·g−1 for microcystin-RR. Most importantly, Fe 3 O 4 @ZIF-8 could be separated from aqueous solution under external magnetic field easily, and maintained good adsorption performance after three cycles. The adsorption mechanism analyzed by FTIR and XPS showed that the adsorption process involved π-π accumulation, complexation reaction and electrostatic interaction. Therefore, the Fe 3 O 4 @ZIF-8 is a kind of potential material which aims to provide a new idea in the field of removing microcystins. [Display omitted] • Fe 3 O 4 @ZIF-8 adsorbed microcystin-RR(MC-RR) rapidly. • Fe 3 O 4 @ZIF-8 can be rapidly separated from water under magnetic field. • The adsorption capacities for MC-RR was 6.1 mg·g−1. [ABSTRACT FROM AUTHOR]

A bacterial strain EMS with the capability of degrading microcystins (MCs) was isolated from Lake Taihu, China. The bacterium was tentatively identified as a Stenotrophomonas sp. The bacterium could completely consume MC-LR and MC-RR within 24 hours at a concentration of 0.7 µg/mL and 1.7 µg/mL, respectively. The degradation of MC-LR and MC-RR by EMS occurred preferentially in an alkaline environment. In addition, mlrA gene involved in the degradation of MC-LR and MC-RR was detected in EMS. Due to the limited literature this gene has rare homologues. Sequencing analysis of the translated protein from mlrA suggested that MlrA might be a transmembrane protein, which suggests a possible new protease family having unique function.

Screening sufficient Fermi level differentiation of photoeletrodes is significantly meaningful for developing high-performance self-powered photoelectrochemical (PEC) sensors. In this work, a dual-photoelectrode self-powered system was fabricated for sensitive detection of Microcystin-RR (MC-RR) by integration of the TiO 2 /S-doped Ti 3 C 2 photoanode and MoS 2 /S-doped Ti 3 C 2 photocathode. The introduction of S-doped Ti 3 C 2 nanosheets synergistically integrated with semiconductors (TiO 2 and MoS 2) could generate the unique Schottky junctions, which could adjust the Fermi energy levels, facilitate the separation of electron-hole pairs and broaden light absorption, leading to high photoelectric conversion efficiency. The electric output of self-powered sensing systems was increased by the substantial inherent bias between the Fermi energy levels of various photoelectrodes and the complementary functions of Schottky junctions, which provided a necessary foundation for the development of sensitive sensors. After the immobilization of the MC-RR aptamer, a novel signal-off dual-photoelectrode self-powered sensor was constructed for sensitive detection of MC-RR based on steric hindrance effect. Moreover, the as-fabricated sensor exhibited prominent analytical performance including wide detection range (10−16 M to 10−9 M), low detection limit (3.4 × 10−17 M), good selectivity, stability and reproducibility, so as to be successfully applied to real sample analysis. The designing ideas of the proposed S-doped Ti 3 C 2 MXene-based Schottky junctions can provide a foothold for the innovative construction of dual-photoelectrode internal-driven self-powered sensing platforms with satisfactory performance. [Display omitted] • S-doping Ti 3 C 2 and Schottky junctions construction were realized simultaneously by one step method. • TiO 2 /S–Ti 3 C 2 and MoS 2 /S–Ti 3 C 2 were applied to construct a dual-photoelectrode self-powered sensor for MC-RR assay. • The introduction of S-doped MXene could enhance photoelectric performance and provide sufficient Fermi level differentiation. • The proposed sensor exhibited excellent analytical performance for MC-RR assay. • The sensing platform was successfully applied to evaluate MC-RR in real samples. [ABSTRACT FROM AUTHOR]

ABSTRACT Microcystins (MCs) are common toxins produced by freshwater cyanobacteria, and they represent a potential health risk to aquatic organisms and animals, including humans. Specific inhibition of protein phosphatases 1 and 2A is considered the typical mechanism of MCs toxicity, but the exact mechanism has not been fully elucidated. To further our understanding of the toxicological mechanisms induced by MCs, this study is the first to use a chemical proteomic approach to screen proteins that exhibit special interactions with MC-arginine-arginine (MC-RR) from zebrafish ( Danio rerio) liver. Seventeen proteins were identified via affinity blocking test. Integration of the results of previous studies and this study revealed that these proteins play a crucial role in various toxic phenomena of liver induced by MCs, such as the disruption of cytoskeleton assembly, oxidative stress, and metabolic disorder. Moreover, in addition to inhibition of protein phosphate activity, the overall toxicity of MCs was simultaneously modulated by the distribution of MCs in cells and their interactions with other target proteins. These results provide new insight into the mechanisms of hepatotoxicity induced by MCs. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1206-1216, 2016. [ABSTRACT FROM AUTHOR]

Bench-scale tests were conducted to investigate the ozonation of Microcystin (MC)-RR obtained from cyanobacterial blooms in this study. The effects of ozone dose, initial MC-RR concentration, solution pH, and coexisting anions on the MC-RR ozonation kinetics were evaluated. Results showed that the MC-RR ozonation well followed the pseudo-first-order degradation kinetics under different experimental conditions. At pH 7 and 461.5 μg/L MC-RR, the degradation rate constant dramatically increased from 0.0125 to 0.0623 min−1with the increase of the ozone dose from 0.31 to 1.35 mg/L, but was not significantly affected by the initial MC-RR concentration. Typically, an acidic condition favored the MC-RR degradation. As the pH increased from 3.1 to 10.1, the rate constant decreased from 0.1906 to 0.0102 min−1at an O3dose of 0.82 mg/L. Different inorganic anions exhibited different behaviors in the MC-RR degradation.slightly enhanced the decomposition, while, Cl−, andslowed the degradation to different degrees. Particularly, the inhibiting effect ofwas significant, probably due to its scavenging effect. These results demonstrated that ozonation appears to be a promising treatment method in the removal of MC-RR from water sources. [ABSTRACT FROM PUBLISHER]

Microcystin-RR (MC-RR) is a dominant variant of microcystin (MC) worldwide. We previously isolated Sphingopyxis sp. USTB-05, which can efficiently biodegrade MC-RR. At least three enzymes encoded by MC-degrading genes are involved. Based on the successful expression of the first gene USTB- 05- A, the second ( USTB- 05- B, KC513423) and third ( USTB- 05- C, KC573527) genes involved in the biodegradation of MC-RR were further cloned from Sphingopyxis sp. USTB-05 and expressed in Escherichia coli BL21 (DE3). After purification, the MC-degrading enzymes encoded by these genes were used for the catalytic degradation of MC-RR. The results demonstrated that the second enzyme encoded by USTB- 05- B could convert linear MC-RR to a tetrapeptide by breaking the Ala-Arg bond. The third enzyme encoded by USTB- 05- C could cleave Adda-Glu peptide bonds of both linear MC-RR and the tetrapeptide of Adda-Glu-Mdha-Ala, producing Adda as their common product. These findings will help better understand the biodegradation mechanism of MCs by Sphingopyxis sp. USTB-05. [ABSTRACT FROM AUTHOR]

Cyanobacterial bloom, a common phenomenon nowadays often results in the depletion of dissolved oxygen (hypoxia) and releases microcystin-RR (MC-RR) in the water. Information on the combined effects of MC-RR and hypoxia on the goldfish is lacking, therefore, this study is aimed at evaluating the effect of two doses of MC-RR on the antioxidants and globin mRNA of goldfish under normoxia, hypoxia and reoxygenation. The result showed that MC-RR at both doses (50 and 200μgkg−1 body weight) significantly (p<0.05) induced superoxide dismutase activities in the liver and kidney but catalase activities and total antioxidant capacity were low in these organs during hypoxia and reoxygenation compared to normoxia and control. Myoglobin and neuroglobin mRNAs in MC-RR group were significantly induced in the brain only and are believed to protect the brain from oxidative damage. However, other organs were unprotected and extensive damage was observed in the liver cells. Our results clearly demonstrated that MC-RR and hypoxia-reoxygenation transitions were synergistically harmful to the goldfish and could impair its adaptation to hypoxia, especially during reoxygenation. [ABSTRACT FROM AUTHOR]

Microcystins (MCs) are well-known cyanobacterial toxins produced in eutrophic waters and can act as potential carcinogens and have caused serious risk to human health. However, pleiotropic even paradoxical actions of cells exposure to MCs have been reported, and the mechanisms of MC-induced tumorigenesis and apoptosis are still unknown. In this study, we performed the first comprehensive in vitro investigation on carcinogenesis associated with nuclear factor kappa B (NF-κB) and its downstream genes in HeLa cells (Human cervix adenocarcinoma cell line from epithelial cells) exposure to MC-RR. HeLa cells were treated with 0, 20, 40, 60, and 80 µg/mL MC-RR for 4, 8, 12, and 24 h. HeLa cells presented dualistic responses to different doses of MCs. CCK8 assay showed that MC-RR exposure evidently enhanced cell viability of HeLa cells at lower MCs doses. Cell cycle and apoptosis analysis revealed that lower MCs doses promoted G1/S transition and cell proliferation while higher doses of MCs induced apoptosis, with a dose-dependent manner. Electrophoretic mobility shift assay (EMSA) revealed that MC-RR could increase/decrease NF-κB activity at lower/higher MC-RR doses, respectively. Furthermore, the expression of NF-κB downstream target genes including c-FLIP, cyclinD1, c-myc, and c-IAP2 showed the same variation trend as NF-κB activity both at mRNA and protein levels, which were induced by lower doses of MC-RR and suppressed by higher doses. Our data verified for the first time that NF-κB pathway may mediate MC-induced cell proliferation and apoptosis and provided a better understanding of the molecular mechanism for potential carcinogenicity of MC-RR. [ABSTRACT FROM AUTHOR]

Microcystin-RR (MC-RR) has been suggested to induce apoptosis in tobacco BY-2 cells through mitochondrial dysfunction including the loss of mitochondrial membrane potential (Δ Ψ m ). To further elucidate the mechanisms involved in MC-RR induced apoptosis in tobacco BY-2 cells, we have investigated the role of mitochondrial electron transport chain (ETC) as a potential source for reactive oxygen species (ROS). Tobacco BY-2 cells after exposure to MC-RR (60 mg/L) displayed apoptotic changes in association with an increased production of ROS and loss of Δ Ψ m . All of these adverse effects were significantly attenuated by ETC inhibitors including Rotenone (2 μmol/L, complex I inhibitor) and antimycin A (0.01 μmol/L, complex III inhibitor), but not by thenoyltrifluoroacetone (5 μmol/L, complex II inhibitor). These results suggest that mitochondrial ETC plays a key role in mediating MC-RR induced apoptosis in tobacco BY-2 cells through an increased mitochondrial production of ROS. [ABSTRACT FROM AUTHOR]

Highlights: [•] A LC–MS/MS method for MC-RR and metabolites in plasma and bile was developed and validated. [•] Liquid–liquid and solid-phase extraction maximally enhance responses of analytes. [•] Limited biological liquid samples are important in the detoxification of MC-RR. [•] The developed assay was successfully utilized to examine toxicokinetics of MCs in plasma and bile. [ABSTRACT FROM AUTHOR]

Abstract: Microcystin-LR (MC-LR) and microcystin-RR (MC-RR) were oxidized and detoxified by improved ozonation using a titanium dioxide (TiO2) catalyst. Experimental results reveal that TiO2 significantly enhances the rate of degradation of MCs by increasing the rate of production of hydroxyl radicals (OH ) by initiating the decomposition of ozone on the catalyst surface. At a pH of 7, through the use of 1.0 O3-mg/L (2.1×10−5 M) and 500mg/L TiO2, the ratio (Rct ) between OH and ozone concentration increases from 2.09×10−8 to 117.10×10−8. Also, TiO2 increases the overall reaction rate. The overall rate constant (koverall ) increases is most increased using 500mg-TiO2/L, which increases the koverall value by more than fivefold. Catalytic ozonation is an effective means of oxidation method in reducing the toxic and mutagenic activities of MCs. An Ames test revealed that MC-LR exhibits positive mutagenic activity in the Salmonella/microsome assay with strains TA98 and TA100 in the absence and presence of S9. However, based on the mutagenic activity of MC-LR during oxidation, catalytic ozonation may either increase or reduce the toxic response of test samples. Additionally, applying ozone couples with high TiO2 dosages reduces mutagenicity, whereas applying fixed 0.5mg-O3/L and TiO2 dosages of lower than 50mg/L increases the mutagenicity of oxidized MC-LR. The mutagenic effects of the test samples are dominated by TiO2 dosage and reaction time, and possibly generate by-products that may change the mutagenic properties of MC-LR. Similar to the results of the Ames test, the results of the Microtox test also reveal that the catalytic ozonated samples exhibit greatly reduced toxicity and markedly lower residual toxicity than the original samples. [Copyright &y& Elsevier]

Abstract: Enzymes encoded by genes biodegrading microcystins (MCs) can help reveal the function of genes and biodegradation pathway of MCs. Here the first and important gene (USTB-05-A, 1,008bp) involved in biodegradation of microcystin-RR (MC-RR) was cloned from Sphingopyxis sp. USTB-05 and firstly expressed in Escherichia coli BL21 (DE3) with an expression vector of pGEX4T-1 successfully. The nucleotide sequences of cloned USTB-05-A possessed 92.5% homology to that of mlA reported in Sphingomonas sp. strain ACM-3962. The deduced amino acid sequences containing the cleavage sites of 26th (alanine) and 27th (leucine) showed 83% identical to that of MlrA. The cell-free extract (CE) of recombinant E. coli BL21 (DE3) containing USTB-05-A had high activity for biodegrading MC-RR. Initial MC-RR of 40mgL−1 was completely biodegraded under total protein of 350mgL−1 within 0.25h. A product derived from MC-RR appeared distinctly with the decrease of MC-RR peak on the profile of HPLC. The product (m/z 1056.5) had molecular weight of 18 higher than that of MC-RR (m/z 1038.7). The findings provided the positive evidences that biodegradation of MC-RR began with the breakage of cyclic MC-RR and then it was converted to linear MC-RR as the first product catalyzed by first enzyme of Sphingopyxis sp. USTB-05. [Copyright &y& Elsevier]

Microcystins (cyclic heptapeptides), produced by a number of freshwater cyanobacteria, are of health concern in potable water supplies. In this article, the adsorptive removal of microcystin-RR (MCRR) from the aqueous solution by a low-cost adsorbent, peat, was investigated. The BET surface area of peat was found to be 12.134 m2/g. The adsorption process was pH dependent, with maximum adsorption occurring at pH 3. Kinetic studies revealed that the adsorption of MCRR onto peat was a rapid process. The adsorption capacity (Qmax) as revealed by the Langmuir model was found to be 286 μg/g at pH 3. Among various desorption media studied, strong alkali solutions (2 N NaOH) showed the highest desorption (97%). Thus, peat has potential to be used as an adsorbent for the removal of the cyanotoxin, MCRR, from drinking water. [ABSTRACT FROM AUTHOR]

A bacterial strain EMS with the capability of degrading microcystins (MCs) was isolated from Lake Taihu, China. The bacterium was tentatively identified as a Stenotrophomonas sp. The bacterium could completely consume MC-LR and MC-RR within 24 hours at a concentration of 0.7 μg/mL and 1.7 μg/mL, respectively. The degradation of MC-LR and MC-RR by EMS occurred preferentially in an alkaline environment. In addition, mlrA gene involved in the degradation of MC-LR and MC-RR was detected in EMS. Due to the limited literature this gene has rare homologues. Sequencing analysis of the translated protein from mlrA suggested that MlrA might be a transmembrane protein, which suggests a possible new protease family having unique function. [ABSTRACT FROM AUTHOR]

Cyanobacterial species commonly occur in the phytoplankton of freshwater lakes and sometimes develop as toxin-producing blooms. Microcystis is one of the most common genera of freshwater cyanobacteria and is often the dominating phytoplankton of eutrophic lakes all over the world. In eutrophic lakes, large amounts of Microcystis may overwinter in the sediment and re-inoculate the water column in spring. In most cases, the overwintering pelagic population—if it exists—is small, and its role in re-inoculation has not been clear yet. In December 2005, we found large amounts of Microcystis on the surface, frozen in the ice cover in a eutrophic pond (Pond Hármashegy, Hungary). We identified the Microcystis species and investigated the viability and the toxicity of the frozen cells. The dominant species in the bloom samples was Microcystis viridis. Viability tests showed that the colonies isolated from the ice cover were composed of living cells. The isolated strain was found toxic, we analyzed the microcystin composition in the frozen planktonic Microcystis mass; in the investigated samples microcystin-RR was the main cyanotoxin. [ABSTRACT FROM AUTHOR]

Abstract: Microcystins (MCs), produced by blue-green algae, are one of the most common naturally occurring toxins found in natural environment. The presence of MCs in drinking water sources poses a great threat to people''s health. In this study, the degradation behavior of microcystin-RR on boron-doped diamond (BDD) electrode was investigated under galvanostatic conditions. Such parameters as reaction time, supporting electrolyte and applied current density were varied in order to determine their effects on this oxidation process. The experimental results revealed the suitability of electrochemical processes employing BDD electrode for removing MC-RR from the solution. However, the efficient removal of MC-RR only occurred in the presence of sodium chloride that acted as redox mediators and the reaction was mainly affected by the chloride concentration ( c NaCl) and applied current density (I appl). Full and quick removal of 0.50μg/ml MC-RR in solution was achieved when the operating conditions of c NaCl and I appl were 20mM and 46.3mA/cm2, or 35mM and 18.2mA/cm2 respectively. The kinetics for MC-RR degradation followed a pesudo-first order reaction in most cases, indicating the process was under mass transfer control. As a result of its excellent performance, the BDD technology could be considered as a promising alternative to promote the degradation of MC-RR than chlorination in drinking water supplies. [Copyright &y& Elsevier]

Electrokinetic sample extraction and enrichment is introduced as a newly developed concept for the analysis of substances in sludge-type or paste-like matrices. It is based on electrokinetic transport phenomena as electromigration and electroosmosis occurring when an electrical field is applied to the fresh, wet samples. Problems usually associated to sample drying can be avoided, e.g., losses of volatile analytes or contamination. We have designed and built a suitable apparatus for electrokinetic sample extraction and enrichment. Appropriate operating conditions (field strength, buffer composition, concentration, and volume) were identified in experiments with an artificial sludge model and real-world lake sediments. A proof of principle of the method was provided by the electromigrative extraction and online enrichment on a solid-phase sorbent disk of an azo dye from a diatomaceous earth slurry. Electroosmotic extraction and enrichment of a cyanobacterial hepatotoxin at trace levels was finally investigated as an application example using lake sediments. Rather clean extracts were obtained even with high organic content sediment samples, as shown by high-performance liquid chromatography with diode array detection. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

In order to evaluate the microcystin removal efficiency of Fenton oxidation, experiments were performed to investigate the destruction of microcystin-RR (MC-RR) in water. The results indicated that the optimal process parameters were determined as follows: 1.5mmol/L H2O2, 0.10mmol/L Fe2+, reaction temperature 25±1°C, pH 3¿4 and 30min reaction time. Under the optimal conditions, the molar ratio of MC-RR:H2O2:Fe2+ was 1:1071:71 and the destruction efficiency of MC-RR was higher than 99%. The initial phase of destruction process followed the pseudo-first order kinetics, and the destruction mechanism was primarily facilitated by the hydroxyl radical oxidation. [Copyright &y& Elsevier]

Abstract: Tobacco BY-2 cells were exposed to microcystin-RR (MC-RR) at two concentrations, 60μgmL−1 and 120μgmL−1, to study the changes in morphology and ultrastructure of cells as a result of the exposure. Exposure to the lower concentration for 5d led to typical apoptotic morphological changes including condensation of nuclear chromatin, creation of a characteristic ‘half moon’ structure, and cytoplasm shrinkage and decreased cell volume, as revealed through light microscopy, fluorescence microscopy, and transmission electron microscopy, respectively. Exposure to the higher concentration, on the other hand, led to morphological and ultrastructural changes typical of necrosis, such as rupture of the plasma membrane and the nuclear membrane and a marked swelling of cells. The presence of many vacuoles containing unusual deposits points to the involvement of vacuoles in detoxifying MC-RR. Results of the present study indicate that exposure of tobacco BY-2 cells to MC-RR at a lower concentration (60μgmL−1) results in apoptosis and that to a higher concentration (120μgmL−1), in necrosis. [Copyright &y& Elsevier]

Abstract: Microcystins are heptapeptide toxins produced by cyanobacteria. Microcystin-RR (MC-RR) is a common variant among the 80 variants identified so far. There have been many investigations documenting the toxic effects of microcystins on animals and higher plants, but little is known on the toxic effects of microcystins on algae, especially at molecular level. We studied the effects of MC-RR on gene expression profile of a few antioxidant enzymes and heat shock protein-70 (Hsp70) in Synechocystis sp. PCC6803. After two days post-exposure, a high dose toxin (5 mg/l, about 4.8 × 10−3 mM) significantly increased expression levels of the genes gpx1, sodB, katG, acnB, γ-TMT and dnaK2, while a relatively low dose toxin (1 mg/l, about 9.63 × 10−4 mM) induced a moderate and slow increase of gene expression. Our results indicate that MC-RR could induce the oxidative stress in Synechocystis sp. PCC6803 and the increase in gene expression of antioxidant enzymes and Hsp70 might protect the organism from the oxidative damage. In addition, cell aggregation was observed during the early period of exposure, which might be a specific oxidative stress reaction to MC-RR. [Copyright &y& Elsevier]

Microcystins are a kind of cyclic hepatoxins produced by many species of cyanobacteria. The toxic effects of microcystins on animals and plants have been well studied. However, the reports about the effects of microcystins on microbial cells are very limited. In present paper, Escherichia coli was undertaken to determine the effect of microcystin-RR. These results suggested that microcystin-RR could prolong the growth of E. coli when exposed to high concentrations of microcystin-RR and cause the accumulation of ROS and induce the oxidant stress for a short time. The antioxidant system protects E. coli from oxidative damage. [ABSTRACT FROM AUTHOR]

Microcystins (MC) are frequently present in cyanobacterial blooms in rivers and lakes, increasing the risk of toxicity to both animals and humans. There more than eighty reported microcystins, and the present study was undertaken to determine whether MC-LR and MC-RR can induce different enzyme alterations and histopathological changes in tilapia fish (Oreochromis sp.) exposed to a single intraperitoneal (i.p.) injection of the pure standards (MC-LR and MC-RR) at a dose of 500 µg/kg; the tilapia fish were then observed for seven days. The two MC variants caused significant changes in the activities of acid and alkaline phosphatases (ACP and ALP) in vital organs, showing a different response pattern. The livers and kidneys of fish injected with MC-LR were particularly affected. MC-RR induced a very pronounced increase of ACP in the kidney and a significant increase of ALP in the liver. Both MC variants caused pathological lesions in hepatic tissues, such as megalocytosis, necrotic process, and microvesicular steatosis, particularly in fish treated with MC-LR, and degenerative renal changes, glomerulopathy, were more severe in tilapias exposed to MC-RR. In addition, both microcystins also caused significant myopathy in the heart. In contrast, the gills did not show any change in enzyme activity or histopathological injury. [ABSTRACT FROM AUTHOR]

This study was undertaken to investigate the role of the glutathione-involved detoxifying mechanism in defending the tobacco BY-2 suspension cells against microcystin-RR (MC-RR). Analysis showed that exposure of the cells to different concentrations of MC-RR (0.1, 1 and 10 μg/mL) for 0–6 days resulted in a time and concentration-dependent decrease in cell viability and increase in reactive oxygen species (ROS) content. Reduced glutathione (GSH) and total glutathione (tGSH) content as well as glutathione reductase (GR), glutathione peroxidase (GPX) and glutathione- s-transferase (GST) activities significantly increased after 3–4 days exposure in the highest two concentration treated groups, while decreased until reaching the control values except for GPX at day 6. Oxidized glutathione (GSSG) content markedly increased compared with control in high concentration MC-RR treated group after 6 days exposure. The GSH/GSSG ratio was much higher than control in 10 μg/mL MC-RR treated group at day 4, but after 6 days exposure, the ratios in all treated groups were lower than that of the control group. [ABSTRACT FROM AUTHOR]

Abstract: The persistence time and risk of microcystin-RR (MC-RR) in cropland via irrigation were investigated under laboratory conditions. In order to evaluate the efficiency of the potential adsorption and biodegradation of MC-RR in cropland and the persistence time of MC-RR for crop irrigation, high performance liquid chromatography (HPLC) was used to quantify the amount of MC-RR in solutions. Our study indicated that MC-RR could be adsorbed and biodegraded in cropland soils. MC-RR at 6.5mg/L could be completely degraded within 6 days with a lag phase of 1–2 days. In the presence of humic acid, the same amount of MC-RR could be degraded within 4 days without a lag phase. Accordingly, the persistence time of MC-RR in cropland soils should be about 6 days. This result also suggested the beneficial effects of the organic fertilizer utilization for the biodegradation of MC-RR in cropland soils. Our studies also demonstrated that MC-RR at low concentration (<10μg/L) could accelerate the growth of plants, while high concentration of MC-RR (>100μg/L) significantly inhibited the growth of plants. High sensitivity of the sprouting stage plants to MC-RR treatments as well as the strong inhibitory effects resulting from prolonged irrigation further indicated that this MC-RR growth-inhibition may vary with the duration of irrigation and life stage of the plants. [Copyright &y& Elsevier]

Microcystins are a kind of cyclic hepatotoxins produced by many cyanobacterial species. Many works have been done concerning the toxic effects of microcystins on animals and plants. However, the reports about their effects on microbial cells are very limited. In the present paper, Bacillus subtilis (B. subtilis) was used to determine the dose- and time-effect of microcystin-RR, and the results showed that the activity of antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT) was significantly increased to that of control, when exposed to 5 or 10 μg/ml microcystin-RR for I h. The contents of thiobarbituric acid-reactive sub-stances (TBARS) and glutathione (GSH) as well as glutathione reductase (GR) activity were obviously increased only when exposed to 10 μg/ml microcystin-RR. For the time-effect of microcystin-RR on B. subtilis, the activities of antioxidant enzymes including SOD and CAT as well as GR activity and TBARS, GSH contents in B. subtilis were at first significantly increased, and then subsequently decreased. These results suggested that microcystin-RR could induce the oxidative stress of B. subtilis for a short period. The antioxidant system protects B. subtilis from oxidative damage. [ABSTRACT FROM AUTHOR]

Abstract: Our previous studies showed that microcystin-RR could induce oxidative damage in plant cells as they do with animal cells. However, whether microcystin can induce plant cell apoptosis is still unknown. In this study, the morphological changes of tobacco BY-2 suspension cells exposed to microcystin-RR were observed under light microscopy and transmission electron microscopy, and apoptosis was clearly distinguished by intense perinuclear chromatin margination, condensation of nuclear chromatin after 6d exposure of 50mg/L (about 50μM) microcystin-RR. We also found that microcystin-RR can induce tobacco cell apoptosis in a dose- and time-dependent manner with flow cytometry analysis. Our study provides the first evidence that microcystins can induce plant cell apoptosis. [Copyright &y& Elsevier]

Abstract: The production of cyanobacterial toxins microcystins (MCs) by cyanobacterial bloom which may promote the growth of tumor in human liver is a growing environmental problem worldwide. In this paper, the adsorption of MC-RR and LR, which were extracted from cyanobacterial cells in Dianchi Lake in China, by carbon nanotubes (CNTs), wood-based activated carbon (ACs) and clays were investigated. Compared with ACs and clay materials of sepiolite, kaolinite and talc tested, CNTs were found to have a strong ability in the adsorption of MCs. At the concentrations of 21.5mgl−1 MC-RR and 9.6mgl−1 MC-LR in 50mmol phosphate buffer solution (pH 7.0), the adsorption amounts of MCs by CNTs with the range of outside diameter from 2 to 10nm were 14.8 and 5.9mgg−1, which were about four times higher than those by other adsorbents tested. It was shown that with the decrease of CNTs outside diameters from 60 to 2nm, the adsorption amount of MCs was apparently increased, however the size of CNTs particles formed in solution declined. This result implies that the size of CNTs tube pore that is fit for the molecular dimension of MCs plays a dominant role. Furthermore the specific surface area of CNTs was also found to be a factor in the adsorption of MCs. The results suggested that the selection of suitable size of CNTs as a kind of adsorbent is very important in the efficient eliminating MCs from drinking water in future. [Copyright &y& Elsevier]

Abstract: Microcystins are cyclic heptapeptide hepatoxins produced by many species of cyanobacteria. The toxic effects and mechanism of microcystins on animals have been well studied both in vivo and in vitro. It was also reported that microcystins had adverse effects on plants. However, to our knowledge, there is no information about the toxic effects and mechanism of microcystins on plant suspension cells. In this study, Arabidopsis thaliana suspension cells were exposed to a range dose of microcystin-RR. Lipid peroxidation, a main manifestation of oxidative damage, was studied and a time- and dose-dependent increase in malondiadehyde was observed. In contrast, glutathione (GSH) levels in the cells decreased after 48h treatment with 1 and 5mg/L of microcystin-RR. The activities of superoxide dismutase (SOD) and catalase (CAT) increased significantly after 48h exposure to 1 and 5mg/L of microcystin-RR, but glutathione S-transferase (GST) activity showed no difference compared with the control. These results clearly indicate that microcystin-RR is able to cause oxidative damage in A. thaliana suspension cells. Decrease of GSH content and increases of SOD and CAT activities reveal that the antioxidant system may play an important role in eliminating or alleviating the toxicity of microcystin-RR. The possible toxicity mechanism of microcystin-RR on the A. thaliana suspension cells is also discussed in this paper. [Copyright &y& Elsevier]

Abstract: Microcystins are cyclic heptapeptide hepatoxins produced by cyanobacteria. It has been shown that microcystins have adverse effects on animals and on plants as well. Previous researches also indicated that microcystins were capable of inducing oxidative damage in animals both in vivo and in vitro. In this study, tobacco BY-2 suspension cell line was applied to examine the effects of microcystin-RR on plant cells. Cell viability and five biochemical parameters including reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPX) and peroxide dismutase (POD) were investigated when cells were exposed to 50mg/L microcystin-RR. Results showed that microcystin-RR evoked decline of the cell viability to approximately 80% after treating for 144h. ROS levels, POD and GPX activities of the treated cells were gradually increased with a time dependent manner. Changes of SOD and CAT activities were also detected in BY-2 cells. After 168h recovery, ROS contents, POD, GPX and CAT activities returned to normal levels. These results suggest that the microcystin-RR can cause the increase of ROS contents in plant cells and these changes led to oxidant stress, at the same time, the plant cells would improve their antioxidant abilities to combat mirocystin-RR induced oxidative injury. [Copyright &y& Elsevier]

Abstract: A new and efficient method for the degradation of microcystins (one family of blue algal toxins) was developed and studied. Microcystins (MCs) in water were directly and effectively removed by active chlorine transformed in situ from the naturally existing Cl− in water resource using electrochemical method. Titanium coated with RuO2 and TiO2 was used as the anode. Microcystin-RR (MCRR) and Microcystin-LR (MCLR) were chosen as the model compounds of MCs. The results suggested that 20.87mgl−1 MCs (12.58mgl−1 MCRR and 8.29mgl−1 MCLR) in aqueous solution with 1.85mM Cl− could be synchronously decomposed within 15min electrolysis under the condition of the current density 8.89mAcm−2, 20°C and pH 7.00. The qualitative analysis showed that the heptapetide ring and the Adda group of both treated MCs were changed. The results also indicated that the removal rates of both MCs increased with the increasing of chloride concentration and applied current density, but decreased with the increasing of initial concentration of MCs and initial pH of electrolyte. In the absence of Cl−, only a small fraction of both MCs were decomposed by direct anodic oxidation, while their almost complete removals could be obtained in the case of indirect electrooxidation with in situ electrogenerated active chlorine from Cl− in water. [Copyright &y& Elsevier]

Abstract: The occurrence of the microcystins in the water bodies, especially in drinking water resources, has received considerable attentions. In situ chemical oxidation is a promising cost-effective treatment method to remove MC from water body. This research investigated the reaction kinetics of the oxidation of MCRR by permanganate. Experimental results indicate that the reaction is second order overall and first order with respect to both permanganate and MCRR, and has an activation energy of 18.9kJ/mol. The second-order rate constant ranges from 0.154 to 0.225l/mg/min at temperature from 15 to 30°C. The MCRR degradation rates can be accelerated through increasing reaction temperature and oxidant concentration. The reaction under acid conditions was slightly faster than under alkaline conditions. The half-life of the reaction was less than 1min, and more than 99.5% of MCRR was degraded within 10min. [Copyright &y& Elsevier]

Microcystins, one type of the cyanobacterial toxins, show a broad range of hazardous effects on other organisms. Most of the researches on the toxic effects of microcystins have involved in animals and higher plants. Little work, however, has been done on evaluating the mechanisms of microcystin toxicity on algae. In this study, the toxicological effects of microcystin-RR (MC-RR) on the cyanobacteriumSynechococcus elongatuswere investigated. For this purpose, six physio-biochemical parameters (cell optical density, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST)) were tested in algal cells when exposed to 100µg-1 microcystin-RR. The results showed that the growth ofSynechococcus elongatus(expressed as optical density) was significantly inhibited compared with the control. At the same time, the treated algae exhibited a pronounced increase in production of ROS and MDA after 6 days exposure to microcystin-RR. Significant changes in GSH levels and GSH-Px, GSH activities were also detected in algal cells, with higher values being observed in the toxin treated algae after 6 days exposure. GST activities in the treated algae exhibited a decline after exposure and rapid augmentation on day 3, thereafter, they kept at a high level when compared to the control group. GSH contents and GSH-Px activities were also significantly raised in the toxin-treated algae cells from day 3, but they showed a sharp decrease on day 4, which was the onward of cell proliferation. These results suggested that oxidative stress manifested by elevated ROS levels and MDA contents might be responsible for the toxicity of microcystin toSynechococcus elongatusand the algal cells could improve their antioxidant ability through the enhancement of enzymatic and non-enzymatic preventive substances. [ABSTRACT FROM AUTHOR]

The cyclic peptide toxins microcystins and nodularins are the most common and abundant cyanotoxins present in diverse water systems. They have been the cause of human and animal health hazards and even death. Over 60 microcystin variants have been reported so far. We report here the results of our study on comparative toxicity evaluation of three most predominant microcystins, MC-LR, MC-RR and MC-YR in mice. The mice were administered one LD50 dose of MC-LR, RR and YR (43, 235.4 and 110.6 μg/kg body weight, respectively), and biochemical and histological variables were determined at 30 min post-treatment and mean time to death (MTD). Significant increase in liver body weight index was induced by all three variants. There was marginal increase in serum levels of hepatic enzymes viz. AST, ALT and γ-GT at 30 min post-treatment but 3–4 fold increase was observed at MTD. In contrast, enhanced LDH leakage, DNA fragmentation and depletion of hepatic glutathione was observed at 30 min post treatment in all three variants. There was no change in levels of serum protein, albumin and albumin/globulin ratio. Liver histology showed time dependent severe pathological lesions like congestion, haemorrhage, portal mononuclear cell infiltration and obliteration of chromatin material. Lung lesions were predominantly in bronchi and parenchyma. Though qualitatively lesions were identical in all three microcystin variants, degree of liver and lung lesions varied quantitatively with the toxin. The breathing pattern and respiratory frequency of the mice after i.p. administration of the toxin showed uniform pattern for 90 min followed by abrupt change in the respiratory pattern and instantaneous death. Based on biochemical and histological studies, MC-LR was found to be the most potent toxin followed by MC-YR and MC-RR. [Copyright &y& Elsevier]

Two metabolites of microcystin-LR glutathione conjugate and, microcystin–cysteine conjugate, as well as microcystin-RR (MCRR) are less toxic than microcystin-LR (MCLR). In the present study, we investigated why these compounds are weakly toxic in comparison with MCLR, as the reason is still unknown and no systematic study has so far been carried out for a clarification of this issue. Although they showed almost the same inhibitory activity against protein phosphatases 1 and 2A as MCLR in vitro, the apparent toxicity of these three compounds by intratracheal administration to mice decreased to about 1/12 the level of MCLR at 100 μg/kg. An immunostaining study showed that these conjugates at a sublethal dose of 200 μg/kg were prominently observed in the intestine and kidney, whereas effective accumulation and bleeding were not found in the liver in spite of the larger dosage. As an explanation for these results, there may be two possibilities. First, the transport system to the liver might not function well, and second, transported toxins may be effectively eliminated by an appropriate system such as the GS-X (ATP-dependent glutathione S-conjugate exported) pump. It was concluded that the inhibitory activity against protein phosphatases is not always related to the apparent LD50 level, and that the appearance of toxicity by microcystins depends on the balance between accumulation and metabolism in the liver. [Copyright &y& Elsevier]

Microcystins (MCs) are toxins produced by several cyanobacterial species found worldwide. While MCs have a common structure, the variation of two amino acids in their structure affects their toxicity. As toxicodynamics are very similar between the MC variants, their differential toxicity could rather be explained by toxicokinetic parameters. Microcystin-RR (MC-RR) is the second most abundant congener and induces toxicity through oral exposure. As intestinal permeability is a key parameter of oral toxicokinetics, the apparent permeability of MC-RR across a differentiated intestinal Caco-2 cell monolayer was investigated. We observed a rapid and large decrease of MC-RR levels in the donor compartment. However, irrespective of the loaded concentration and exposure time, the permeabilities were very low from apical to basolateral compartments (from 4 to 15 × 10−8 cm·s−1) and from basolateral to apical compartments (from 2 to 37 × 10−8 cm·s−1). Our results suggested that MC-RR would be poorly absorbed orally. As similar low permeability was reported for the most abundant congener microcystin-LR, and this variant presented a greater acute oral toxicity than MC-RR, we concluded that the intestinal permeability was probably not involved in the differential toxicity between them, in contrast to the hepatic uptake and metabolism. [ABSTRACT FROM AUTHOR]

Microcystins (MCs), produced by Microcystis sp, are the most commonly detected cyanotoxins in freshwater, and due to their toxicity, worldwide distribution, and persistence in water, an improvement in the monitoring programs for their early detection and removal from water is necessary. To this end, we investigate the performance of three covalent organic frameworks (COFs), TpBD-(CF 3 ) 2 , TpBD-(NO 2 ) 2 , and TpBD-(NH 2 ) 2 , for the adsorption of the most common and/or toxic MC derivatives, MC-LR, MC-RR, MC-LA, and MC-YR, from water. While MC-LR and MC-YR can be efficiently adsorbed using all three COF derivatives, high adsorption efficiencies were found for the most lipophilic toxin, MC-LA, with TpBD-(NH 2 ) 2 , and the most hydrophilic one, MC-RR, with TpBD-(NO 2 ). Theoretical calculations revealed that MC-LA and MC-RR have a tendency to be located mainly on the COF surface, interacting through hydrogen bonds with the amino and nitro functional groups of TpBD-(NH 2 ) 2 and TpBD-(NO 2 ) 2 , respectively. TpBD-(NO 2 ) 2 outperforms the adsorbent materials reported for the capture of MC-RR, resulting in an increase in the maximum adsorption capacity by one order of magnitude. TpBD-(NH 2 ) 2 is reported as the first efficient adsorbent material for the capture of MC-LA. Large differences in desorption efficiencies were observed for the MCs with different COFs, highlighting the importance of COF-adsorbate interactions in the material recovery. Herein we show that efficient capture of these toxins from water can be achieved through the proper selection of the COF material. More importantly, this study demonstrates that by careful choice of COF functionalities, specific compounds can be targeted or excluded from a group of analogues, providing insight into the design of more efficient and selective adsorbent materials.