Search Results (88)

Cyanobacterial blooms are an escalating ecological concern driven by eutrophication and climate warming. Bloom-forming cyanobacteria can produce a broad spectrum of bioactive secondary metabolites. Among these, microcystins (MCs) are the most recognised hepatotoxins; however, natural populations of Planktothrix agardhii also synthesise numerous non-ribosomal peptides (NRPs) with poorly understood ecological roles and combined toxic effects. This review demonstrated the role of mixtures of P. agardhii cyanometabolites (oligopeptides and biogenic compounds) in cyanobacterial proliferation, emphasising the rapid evolution of chemotypes. The role of P. agardhii oligopeptides other than MCs in the cyanobacterial toxicity to duckweeds is also discussed. Laboratory experiments indicated that crude extracts containing complex peptide mixtures may inhibit Spirodela polyrhiza growth more strongly than pure MC-LR, suggesting synergistic effects within natural metabolite assemblages. Particular attention is given to variant-specific degradation pathways of MCs within duckweed-associated microbiota. By integrating biochemical, ecological, and microbiological perspectives, this synthesis outlines emerging directions in the study of mixtures of cyanobacterial peptides and other compounds, microbial degraders, and macrophyte-associated bioremediation strategies aimed at mitigating cyanotoxin risks in aquatic environments. Full article

Cyanobacterial blooms are a common water pollution phenomenon worldwide now. Among them, Microcystis blooms occur most frequently internationally, and most of them can produce hepatotoxins—microcystins (MCs). When the bloom occurs in water bodies, common carp, as the top consumers in the aquatic food chain, inevitably ingest a large amount of cyanobacteria. The effects on the intestinal digestion, immunity, and microbiota of the carp remain to be revealed. In the present study, 21-day gavage exposure to Microcystis paste (equivalent to 378.25 μg/kg of MC-LR) was conducted on juvenile carp mainly to investigate the adverse effects of MCs on the fish intestinal digestion, immunity, and microbiota. The results showed that Microcystis exposure caused intestinal barrier damage, intestinal structure destruction, and increased permeability. Analysis of the activities of three main intestinal digestive enzymes showed that Microcystis exposure affected the intestinal digestion of fish. Targeted metabolome analysis and 16S rRNA sequencing showed that the abundance of opportunistic pathogens such as Proteobacteria and Aeromonas increased in the exposed fish, and the contents of intestinal metabolites lipopolysaccharide (LPS) and trimethylamine oxide (TMAO) increased. However, the abundance of Firmicutes and Bacillus that produce short-chain fatty acids (SCFAs) was significantly reduced. These results indicated that Microcystis exposure could imbalance the intestinal flora and increase the abundance of Gram-negative bacteria, thereby activating the inflammatory response in the common carp. In summary, oral Microcystis exposure by the common carp can negatively affect fish digestion, immunity, and flora homeostasis of the fish intestinal tract. This study also provides a theoretical basis for a comprehensive evaluation of the beneficial effects of SCFAs on regulating metabolic disorders, activating lipid catabolism, and nutrient utilization of fish in aquaculture. Full article

Circadian rhythm disruption induced by exposure to light—excessive in duration and intensity (dark deprivation)—and the impact of hepatotoxins are both significant risk factors for liver pathology. The purpose of this research was to evaluate the potentially synergistic effects of continuous lighting and carbon tetrachloride (CCl₄) toxicity on the structural and functional organization and daily (circadian) rhythmicity of the liver in rats, as well as to look at the corrective capability of exogenous melatonin under such influences. The experiment was conducted on 200 outbred 6-month-old Wistar rat males, which were distributed into five groups, including a control (normal light/dark cycle), dark deprivation (constant light), CCl₄ intoxication, and combined exposure to CCl₄ and dark deprivation with or without melatonin administration (0.3 mg/kg). Histological, immunohistochemical (Ki-67, Per2, and Bmal1), biochemical, and ELISA methods were used. Circadian rhythms were analyzed using cosinor. It was shown that dark deprivation and CCl₄ intoxication act synergistically, potentiating liver damage. The most severe necrosis (54.17 ± 9.13%), steatosis (57.85 ± 12.14%), and suppression of regenerative potential (decreased proportion of binucleated hepatocytes to 2.17 ± 0.21%) were observed in the group with combined exposure. This correlated with a substantial decline in melatonin content in blood plasma (7.85 ± 2.1 pg/mL) and a profound disruption in circadian rhythms. Administration of exogenous melatonin exerted pronounced hepatoprotective and chronotropic effects: it significantly reduced pathological changes (necrosis reduced to 16.35 ± 6.17%), stimulated regeneration (binucleated hepatocytes increased to 13.57 ± 0.81%), and restored the circadian rhythms of the studied parameters to levels close to those of the control. The key pathogenetic link in the potentiation of CCl₄ hepatotoxicity under dark deprivation is light-induced deficiency of endogenous melatonin. Exogenous melatonin demonstrated high efficacy in correcting both structural and functional damage and liver desynchronosis, confirming its therapeutic potential under conditions of combined exposure to chronodisruptors and toxins. Full article

Microcystin-LR (MC-LR) is a hepatotoxin produced by toxic cyanobacteria such as Microcystis aeruginosa and it poses significant risks to aquatic organisms and human health. However, research on the long-term effects of environmental MC-LR exposure on lipid metabolism in fish is relatively scarce. This research investigates the effects and underlying mechanisms of chronic (one month) low-dose (3.5 μg/kg) MC-LR exposure in common carp (Cyprinus carpio) by using biochemical assays, histopathology, molecular analyses, and lipidomics. In this study, MC-LR exposure significantly altered serum enzyme activities and lipid profiles, induced hepatic inflammation and lipid accumulation, and disrupted hepatopancreatic structure. Meanwhile, key regulators of lipogenesis, fatty acid β-oxidation, and cholesterol metabolism were dysregulated, indicating enhanced lipid synthesis and impaired catabolism. Elevated oxidative stress and pro-inflammatory cytokines likely contributed to lipid metabolic disturbances, exacerbating the hepatotoxicity of MC-LR. Lipidomics profiling revealed significant disruptions in glycerophospholipids, glycerolipids, and sphingolipids, highlighting impaired lipid homeostasis. This study provides novel insights into the hepatic lipid metabolic disorders induced by MC-LR in fish. Full article

Over the past 15 years, Nodularia spumigena blooms in the Gulf of Gdańsk (southern Baltic Sea) have reached exceptional intensity, accounting for up to 90% of phytoplankton biomass during peak summer periods. Our long-term observations revealed oscillations in blooms intensity, with peak nodularin concentrations (up to 45,000 μg/L) recorded in 2012, 2015, and 2018—the highest levels of this toxin documented to date in both the Baltic Sea and worldwide. An extreme cyanobacterial bloom in 2018, caused by unusually high air and water temperatures, covered almost the whole surface of the Gulf of Gdańsk, causing multi-day closures of bathing areas. During this bloom, high levels of microcystins (up to 6640 μg/L MC-LR) were also detected, as well as the presence of 42 cyanopeptides, mainly anabaenopeptides and spumigins, which were present at concentrations 5–10 times higher than hepatotoxins. Full article

Microcystis aeruginosa is a cyanobacterium frequently associated with toxic blooms in eutrophic freshwater systems. Certain strains produce microcystins (MCs), a group of hepatotoxins with significant ecological and public health implications. In this study, we examined the quantitative response of a temperate native M. aeruginosa strain to combinations of temperature (26, 30, and 36 °C), light intensity (30, 50, and 70 µmol photons·m⁻²·s⁻¹), and N:P ratio (10, 100, 150), using a full-factorial experimental design. Growth parameters (µ, lag phase duration, and maximum cell density), chlorophyll-a production, and MC-LR synthesis were modeled using Gompertz, linear, and dynamic approaches. High temperature and irradiance increased the specific growth rate but decreased final biomass, while elevated N:P ratios shortened the lag phase. MC-LR production peaked under low temperature, low irradiance, and low N:P ratio. Although MC-LR synthesis did not correlate positively with growth rate, and the environmental conditions maximizing growth differed from those enhancing toxin production, a population-level coupling between both processes was observed using the Long model. These findings suggest that MC-LR synthesis in M. aeruginosa is not merely a metabolic by-product of growth, but a context-dependent trait with potential adaptive significance. Full article

Microcystins (MCs), hepatotoxins produced by cyanobacteria, represent a potential threat to aquatic ecosystems and human health. Measuring various environmental and cyanobacterial parameters in water samples can be useful for monitoring water quality and assessing risk but remains a short-term approach. Beyond local risk assessments, estimating global and medium-term levels of freshwater contamination by MC-producing cyanobacteria is challenging in large lakes due to the spatio-temporal variability of their proliferation and the need to multiply sampling dates and locations. In such conditions, a sentinel organism can be valuable for monitoring MCs in situ and providing a time-integrated picture of contamination levels at various stations. We previously assessed the ability of the freshwater bivalves Anodonta anatina and Dreissena polymorpha to act as biointegrators of MCs, even under low exposure levels to cyanobacteria. In this study, through a two-season investigation in several French lakes experiencing moderate cyanobacterial blooms, we evaluated the relevance of various parameters (cyanobacterial density and biovolume, chlorophyll-a, and phycocyanin) as well as the use of bivalves as indicators of medium-term freshwater contamination by MC-producing cyanobacteria. MC concentrations in cyanobacterial biomass (intracellular MCs) and in bivalves (free MCs, being unbound, and total free and protein-bound accumulated MCs) were measured alongside the characterization of phytoplankton communities. Both mussels integrated and highlighted the presence of intracellular MCs in the environment over the period between two successive water samplings, even at low contamination levels, demonstrating their suitability for in situ biomonitoring of MC-producing cyanobacteria. The results are discussed in terms of the strengths and limitations of different parameters for assessing MC contamination levels in waters depending on the objective (managing, preventing, or global evaluation) and the monitoring strategies used. Full article

Hepatoencephalopathy (HE) is a liver disease that can lead to brain pathology and the impairment of human cognitive abilities. The objective assessment of HE disease severity is difficult due to the lack of reliable diagnostic markers. This paper examines the background to the emergence of HE markers and provides a brief overview of research results indicating the diagnostic value of potential markers isolated from a wide range of metabolites analyzed. It has been suggested that metabolites of the glutamate–glutamine (Glu-Gln) cycle, α-ketoglutarate (αKG), and α-ketoglutaramate (αKGM) can act as such markers of HE. The informative value of these markers was revealed during a comparative analysis of the distribution of αKG and αKGM in samples of the blood plasma and tissues (liver, kidneys, and brain) of rats exposed to the strong hepatotoxin thioacetamide (TAA). A comparative analysis of the balance of αKG and αKGM, as well as their ratio (αKG/αKGM) in the examined samples of blood plasma and animal tissues in these models, revealed their diagnostic value for assessing the severity of HE and/or monitoring the recovery process. Full article

Microcystin (MC), a hepatotoxin produced by cyanobacteria, was introduced into the Indian River Lagoon (IRL), Florida, in 2005 through freshwater outflows. Since then, MC has been detected in humans, domestic animals, and wildlife in the lagoon. Potential public health effects associated with MC exposure along the IRL include an increased risk of non-alcoholic liver disease among area residents. Yet, there are limited studies characterizing liver disease, as well as the potential role of MC, in humans and animals in this region. Thus, histopathology reports (n = 133) were reviewed in the stranded common bottlenose dolphin (Tursiops truncatus truncatus) (n = 156, 2005–2024) to describe liver lesions in this important IRL sentinel. Liver and fecal samples (n = 161) from stranded individuals were screened for MC via an enzyme immunoassay (ELISA). These samples were then confirmed via the 2-methyl-3-methoxy-4-phenylbutyric acid technique (MMPB) to evaluate whether liver histopathologic lesions were linked to MC exposure. Minimally invasive MC screening methods were also assessed using respiratory swabs and vapor. Inflammation (24%, n = 32), fibrosis (23%, n = 31), lipidosis/vacuolation (11%, n = 15), and necrosis (11%, n = 14) were the most common liver anomalies observed. These non-specific lesions have been reported to be associated with MC exposure in numerous species in the peer-reviewed literature. Ten bottlenose dolphins tested positive for the toxin via ELISA, including two individuals with hepatic lipidosis, but none were confirmed by MMPB. Thus, this study did not provide evidence for MC-induced liver disease in IRL bottlenose dolphins. Other causes should be considered for the lesions observed (e.g., heavy metals, metabolic disease, and endoparasites). Respiratory swabs require further validation as a pre-mortem MC screening tool in free-ranging wildlife. Full article

Toxigenic cyanobacteria and microcystins in the oligotrophic pelagic zone and mesotrophic bay of Lake Onego—the second largest lake in Europe—were found for the first time. Microscopic analysis revealed that Dolichospermum lemmermannii, D. circinale and D. spiroides dominated in bloom spots in the oligotrophic zone of the lake and D. flos-aquae and Microcystis aeruginosa OKin the eutrophic bay. The abundance of cyanobacteria in bloom spots is potentially hazardous for humans and animals. PCR-analysis showed that mcyA gene involved in microcystin biosynthesis was found in cyanobacteria of the genera Dolichospermum and Microcystis. Five structural variants of intracellular microcystins were detected in a trace amount using high-performance liquid chromatography–mass-spectrometry of high resolution. The most hazardous hepatotoxin, MC-LR, was found only in the eutrophic bay. In the present study, the reasons for the low cyanotoxin content in the phytoplankton dominated by Dolichospermum are discussed. The findings of our study make a significant contribution to the accumulation of facts which state that toxigenic cyanobacterial blooms can occur in large oligotrophic lakes. Full article

Molybdenum (Mo) is an essential element for human life, acting as a cofactor in various enzymes crucial for metabolic homeostasis. This review provides a comprehensive insight into the latest advances in research on molybdenum-containing enzymes and their clinical significance. One of these enzymes is xanthine oxidase (XO), which plays a pivotal role in purine catabolism, generating reactive oxygen species (ROS) capable of inducing oxidative stress and subsequent organ dysfunction. Elevated XO activity is associated with liver pathologies such as non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Aldehyde oxidases (AOs) are also molybdenum-containing enzymes that, similar to XO, participate in drug metabolism, with notable roles in the oxidation of various substrates. However, beneath its apparent efficacy, AOs’ inhibition may impact drug effectiveness and contribute to liver damage induced by hepatotoxins. Another notable molybdenum-enzyme is sulfite oxidase (SOX), which catalyzes the conversion of sulfite to sulfate, crucial for the degradation of sulfur-containing amino acids. Recent research highlights SOX’s potential as a diagnostic marker for HCC, offering promising sensitivity and specificity in distinguishing cancerous lesions. The newest member of molybdenum-containing enzymes is mitochondrial amidoxime-reducing component (mARC), involved in drug metabolism and detoxification reactions. Emerging evidence suggests its involvement in liver pathologies such as HCC and NAFLD, indicating its potential as a therapeutic target. Overall, understanding the roles of molybdenum-containing enzymes in human physiology and disease pathology is essential for advancing diagnostic and therapeutic strategies for various health conditions, particularly those related to liver dysfunction. Further research into the molecular mechanisms underlying these enzymes’ functions could lead to novel treatments and improved patient outcomes. Full article

In the example of a rat model with chronic hepatoencephalopathy (HE), changes in the organ morphology of rats affect the balance of metabolites of the tricarboxylic acid (TCA) cycle and metabolites of the glutamine–glutamate (Gln-Glu) cycle, namely α-ketoglutarate (αKG) and α-ketoglutaramate (αKGM), as well as the enzymes associated with them, ω-amidase (ωA) and glutamine transaminase (GTK). This model of rats was obtained as a result of 2–22 weeks of consumption by animals of hepatotoxin thioacetamide (TAA) added to drinking water at a concentration of 0.4 g/L. The control (n = 26) and TAA-induced (n = 55) groups of rats consisted of 11 cohorts each. The control cohorts consisted of 2–4 rats, and the TAA-induced cohorts consisted of 4–7 individuals. Every two weeks, samples of blood plasma, liver, kidney, and brain tissues were taken from the next cohort of rats (a total of 320 samples). By the end of the experiment, irreversible morphological changes were observed in the organs of rats: the weight of the animals was reduced up to ~45%, the weight of the kidneys up to 5%, the brain up to ~20%, and the weight of the liver increased up to ~20%. The analysis revealed: (i) a decrease in the activity of ωA and GTK in the tissues of the brain, kidneys, and liver of rats with chronic HE (by ~3, 40, and 65% and ~10, 60, and 70%, respectively); and (ii) the appearance of a significant imbalance in the content of metabolites of the Gln-Glu cycle, αKG, and αKGM. It is indicative that a ~1.5–12-fold increase in the level of αKG in the blood plasma and tissues of the organs of rats with chronic HE was accompanied by a synchronous, ~1.2–2.5-fold decrease in the level of αKGM. The data obtained indicate an essential involvement of the Gln-Glu cycle in the regulation of energy metabolism in rats under conditions of chronic HE. Attention is focused on the significance of the αKG/αKGM ratio, which can act as a potential marker for diagnosing the degree of HE development. Full article

Okadaic acids (OAs) are causative agents of diarrhetic shellfish poisoning, produced by the dinoflagellates Dinophysis spp. and Prorocentrum spp. Microcystins (MCs) are cyclic heptapeptide hepatotoxins produced by some cyanobacteria genera, including Microcystis spp. Traditionally, toxicity detection and quantification of these natural toxins were performed using a mouse bioassay (MBA); however, this is no longer widely employed owing to its lack of accuracy, sensitivity, and with regard to animal welfare. Therefore, alternative toxicity analyses have been developed based on MCs’ and OAs’ specific inhibition of protein phosphatase 2A (PP2A), using p-nitrophenylphosphate (p-NPP) as a substrate. The assay is simple, inexpensive, ready for use on site, and can be applied to several samples at once. For OA detection, this assay method is appropriate for widespread application as a substitute for MBA, as evidenced by its alignment with the oral toxicity of MBA. In this review, we summarize the structure and function of PP2A, the inhibitory activities of OAs and MCs against PP2A, and the practical applications of the PP2A assay, with the aim of improving understanding of the PP2A assay as an OAs and MCs detection and quantification method, as well as its suitability for screening before confirmatory chemical analysis. Full article

Chronic liver disease (CLD) affects a significant portion of the global population, leading to a substantial number of deaths each year. Distinct forms like non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (ALD), though they have different etiologies, highlight shared pathologies rooted in oxidative stress. Central to liver metabolism, mitochondria are essential for ATP production, gluconeogenesis, fatty acid oxidation, and heme synthesis. However, in diseases like NAFLD, ALD, and liver fibrosis, mitochondrial function is compromised by inflammatory cytokines, hepatotoxins, and metabolic irregularities. This dysfunction, especially electron leakage, exacerbates the production of reactive oxygen species (ROS), augmenting liver damage. Amidst this, nuclear factor erythroid 2-related factor 2 (NRF2) emerges as a cellular protector. It not only counters oxidative stress by regulating antioxidant genes but also maintains mitochondrial health by overseeing autophagy and biogenesis. The synergy between NRF2 modulation and mitochondrial function introduces new therapeutic potentials for CLD, focusing on preserving mitochondrial integrity against oxidative threats. This review delves into the intricate role of oxidative stress in CLD, shedding light on innovative strategies for its prevention and treatment, especially through the modulation of the NRF2 and mitochondrial pathways. Full article

The rapid rise of microcystins (MCs) poses a serious threat to global freshwater ecosystems and has become an important issue of global public health. MCs have considerable stability and are the most widely distributed hepatotoxins. It cannot only accumulate in aquatic organisms and transfer to higher nutrients and levels, but also be degraded or transferred during the resource utilization of cyanobacteria. No matter which enrichment method, it will lead to the risk of human exposure. This review summarizes the research status of MCs, and introduces the distribution of MCs in different components of aquatic ecosystems. The distribution of MCs in different aquatic organisms was summarized, and the potential risks of MCs in the environment to human safety were summarized. MCs have polluted all areas of aquatic ecosystems. In order to protect human life from the health threats caused by MCs, this paper also proposes some future research directions to promote MCs control and reduce human exposure to MCs. Full article