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Marine Drugs Oct 2022Harmful algal blooms are an increasing worldwide threat to the seafood industry and human health as a consequence of the natural production of biotoxins that can...
Harmful algal blooms are an increasing worldwide threat to the seafood industry and human health as a consequence of the natural production of biotoxins that can accumulate in shellfish. In the Argentine Sea, this has been identified as an issue for the offshore fisheries of Patagonian scallops (), leading to potentially harmful effects on consumers. Here we assess spatial and temporal patterns in marine biotoxin concentrations in Patagonian scallops harvested in Argentinian waters between 2012-2017, based on analyses for paralytic shellfish toxins, lipophilic toxins, and amnesic shellfish toxins. There was no evidence for concentrations of lipophilic or amnesic toxins above regulatory acceptance thresholds, with trace concentrations of pectenotoxin 2, azaspiracid 2 and okadaic acid group toxins confirmed. Conversely, paralytic shellfish toxins were quantified in some scallops. Gonyautoxins 1 and 2 dominated the unusual toxin profiles (91%) in terms of saxitoxin equivalents with maximum concentrations reaching 3985 µg STX eq/kg and with changes in profiles linked in part to seasonal changes. Total toxin concentrations were compared between samples of the adductor muscle and whole tissue, with results showing the absence of toxins in the adductor muscle confirming toxin accumulation in the digestive tracts of the scallops and the absence of a human health threat following the processing of scallop adductor meat. These findings highlight that paralytic shellfish toxins with an unusual toxin profile can occur in relatively high concentrations in whole Patagonian scallops in specific regions and during particular time periods, also showing that the processing of scallops on board factory ships to obtain frozen adductor muscle is an effective management process that minimizes the risk of poisonings from final products destined for human consumption.
Topics: Animals; Humans; Marine Toxins; Okadaic Acid; Saxitoxin; Seafood; Pectinidae
PubMed: 36286458
DOI: 10.3390/md20100634 -
Biomedical and Environmental Sciences :... Jan 2023
Topics: Rats; Animals; Okadaic Acid; PC12 Cells; Triterpenes; tau Proteins; Phosphorylation
PubMed: 36650687
DOI: 10.3967/bes2023.011 -
The Journal of Physiological Sciences :... Jun 2020Tolfenamic acid, a nonsteroidal anti-inflammatory drug, alleviated learning and memory deficits and decreased the expression of specificity protein 1 (SP1)-mediated...
Tolfenamic acid, a nonsteroidal anti-inflammatory drug, alleviated learning and memory deficits and decreased the expression of specificity protein 1 (SP1)-mediated cyclin-dependent kinase-5 (CDK5), a major protein kinase that regulates hyperphosphorylated tau, in Alzheimer's disease (AD) transgenic mice. However, whether tolfenamic acid can regulate the major tau protein kinase, glycogen synthase kinase-3β (GSK-3β), or tau protein phosphatase, protein phosphatase 2A (PP2A), further inhibiting hyperphosphorylation of tau, remains unknown. To this end, tolfenamic acid was administered i.p. in a GSK-3β overactivation postnatal rat model and orally in mice after intracerebroventricular (ICV) injection of okadaic acid (OA) to develop a PP2A inhibition model. We used four behavioural experiments to evaluate memory function in ICV-OA mice. In this study, tolfenamic acid attenuated memory dysfunction. Tolfenamic acid decreased the expression of hyperphosphorylated tau in the brain by inhibiting GSK-3β activity, decreasing phosphorylated PP2A (Tyr307), and enhancing PP2A activity. Tolfenamic acid also increased wortmannin (WT) and GF-109203X (GFX) induced phosphorylation of GSK-3β (Ser9) and prevented OA-induced downregulation of PP2A activity in PC12 cells. Altogether, these results show that tolfenamic acid not only decreased SP1/CDK5-mediated tau phosphorylation, but also inhibited GSK-3β and PP2A-mediated tau hyperphosphorylation in AD models.
Topics: Alzheimer Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Female; Glycogen Synthase Kinase 3 beta; Male; Mice; Mice, Inbred C57BL; Phosphorylation; Protein Phosphatase 2; Rats; Rats, Wistar; ortho-Aminobenzoates; tau Proteins
PubMed: 32517647
DOI: 10.1186/s12576-020-00757-y -
International Journal of Molecular... Feb 2024Three-dimensional (3D) bioprinting is one of the most promising methodologies that are currently in development for the replacement of animal experiments. Bioprinting...
Three-dimensional (3D) bioprinting is one of the most promising methodologies that are currently in development for the replacement of animal experiments. Bioprinting and most alternative technologies rely on animal-derived materials, which compromises the intent of animal welfare and results in the generation of chimeric systems of limited value. The current study therefore presents the first bioprinted liver model that is entirely void of animal-derived constituents. Initially, HuH-7 cells underwent adaptation to a chemically defined medium (CDM). The adapted cells exhibited high survival rates (85-92%) after cryopreservation in chemically defined freezing media, comparable to those preserved in standard medium (86-92%). Xeno-free bioink for 3D bioprinting yielded liver models with high relative cell viability (97-101%), akin to a Matrigel-based liver model (83-102%) after 15 days of culture. The established xeno-free model was used for toxicity testing of a marine biotoxin, okadaic acid (OA). In 2D culture, OA toxicity was virtually identical for cells cultured under standard conditions and in CDM. In the xeno-free bioprinted liver model, 3-fold higher concentrations of OA than in the respective monolayer culture were needed to induce cytotoxicity. In conclusion, this study describes for the first time the development of a xeno-free 3D bioprinted liver model and its applicability for research purposes.
Topics: Animals; Drug-Related Side Effects and Adverse Reactions; Chemical and Drug Induced Liver Injury; Bioprinting; Printing, Three-Dimensional; Tissue Engineering; Tissue Scaffolds
PubMed: 38339088
DOI: 10.3390/ijms25031811 -
Scientific Reports Apr 2024Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease, and it is characterized by the intracellular and extracellular accumulation...
Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease, and it is characterized by the intracellular and extracellular accumulation of α-synuclein (α-syn) and Tau, which are major components of cytosolic protein inclusions called Lewy bodies, in the brain. Currently, there is a lack of effective methods that preventing PD progression. It has been suggested that the plasminogen activation system, which is a major extracellular proteolysis system, is involved in PD pathogenesis. We investigated the functional roles of plasminogen in vitro in an okadaic acid-induced Tau hyperphosphorylation NSC34 cell model, ex vivo using brains from normal controls and methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, and in vivo in a widely used MPTP-induced PD mouse model and an α-syn overexpression mouse model. The in vitro, ex vivo and in vivo results showed that the administered plasminogen crossed the blood‒brain barrier (BBB), entered cells, and migrated to the nucleus, increased plasmin activity intracellularly, bound to α-syn through lysine binding sites, significantly promoted α-syn, Tau and TDP-43 clearance intracellularly and even intranuclearly in the brain, decreased dopaminergic neurodegeneration and increased the tyrosine hydroxylase levels in the substantia nigra and striatum, and improved motor function in PD mouse models. These findings indicate that plasminogen plays a wide range of pivotal protective roles in PD and therefore may be a promising drug candidate for PD treatment.
Topics: Animals; Mice; alpha-Synuclein; Disease Models, Animal; DNA-Binding Proteins; Dopamine; Neurodegenerative Diseases; Parkinson Disease; Plasminogen; Serine Proteases; tau Proteins; Dopaminergic Neurons
PubMed: 38615036
DOI: 10.1038/s41598-024-59090-8 -
Toxins Oct 2023For the purpose of assessing human health exposure, it is necessary to characterize the toxins present in a given area and their potential impact on commercial species....
For the purpose of assessing human health exposure, it is necessary to characterize the toxins present in a given area and their potential impact on commercial species. The goal of this research study was: (1) to screen the prevalence and concentrations of lipophilic toxins in nine groups of marine invertebrates in the northwest Iberian Peninsula; (2) to evaluate the validity of wild mussels () as sentinel organisms for the toxicity in non-bivalve invertebrates from the same area. The screening of multiple lipophilic toxins in 1150 samples has allowed reporting for the first time the presence of 13-desmethyl spirolide C, pinnatoxin G, okadaic acid, and dinophysistoxins 2 in a variety of non-traditional vectors. In general, these two emerging toxins showed the highest prevalence (12.5-75%) in most of the groups studied. Maximum levels for 13-desmethyl spirolide C and pinnatoxin G were found in the bivalves (21 µg kg) and (63 µg kg), respectively. However, mean concentrations for the bivalve group were shallow (2-6 µg kg). Okadaic acid and dinophysistoxin 2 with lower prevalence (1.6-44.4%) showed, on the contrary, very high concentration values in specific species of crustaceans and polychaetes (334 and 235 µg kg, respectively), to which special attention should be paid. Statistical data analyses showed that mussels could be considered good biological indicators for the toxicities of certain groups in a particular area, with correlations between 0.710 (for echinoderms) and 0.838 (for crustaceans). Polychaetes could be an exception, but further extensive surveys would be needed to draw definitive conclusions.
Topics: Animals; Humans; Okadaic Acid; Marine Toxins; Shellfish; Shellfish Poisoning; Chromatography, Liquid; Tandem Mass Spectrometry; Bivalvia; Mytilus
PubMed: 37999494
DOI: 10.3390/toxins15110631 -
Life (Basel, Switzerland) Dec 2022Toxins of the OA-group (okadaic acid, OA; dinophysistoxin-1, DTX-1) are the most prevalent in the fjords of southern Chile, and are characterized by their potential...
Toxins of the OA-group (okadaic acid, OA; dinophysistoxin-1, DTX-1) are the most prevalent in the fjords of southern Chile, and are characterized by their potential harmful effects on aquatic organisms. The present study was carried out to determine the acute toxicity of OA/DTX-1 on oxidative stress parameters in medaka () larvae. Medaka larvae were exposed to different concentrations (1.0-30 μg/mL) of OA/DTX-1 for 96 h to determine the median lethal concentration. The LC value after 96 h was 23.5 μg/mL for OA and 16.3 μg/mL for DTX-1 (95% confidence interval, CI was 22.56, 24.43 for OA and 15.42, 17.17 for DTX-1). Subsequently, larvae at 121 hpf were exposed to acute doses (10, 15 and 20 μg/mL OA and 5.0, 7.5 and 11.0 μg/mL DTX-1) for 96 h and every 6 h the corresponding group of larvae was euthanized in order to measure the activity levels of biochemical biomarkers (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPx; and glutathione reductase, GR) as well as the levels of oxidative damage (malondialdehyde, MDA; and carbonyl content). Our results showed that acute doses caused a decrease in SOD (≈25%), CAT (≈55%), and GPx and GR (≈35%) activities, while MDA levels and carbonyl content increased significantly at the same OA/DTX-1 concentrations. This study shows that acute exposure to OA-group toxins tends to simultaneously alter the oxidative parameters that induce sustained morphological damage in medaka larvae. DTX-1 stands out as producing greater inhibition of the antioxidant system, leading to increased oxidative damage in medaka larvae. Considering that DTX-1 is the most prevalent HAB toxin in southern Chile, these findings raise the possibility of an important environmental impact on the larval stages of different fish species present in the southern fjords of the South Pacific.
PubMed: 36675964
DOI: 10.3390/life13010015 -
Comparative Biochemistry and... Sep 2023Globally around 24 million elderly population are dealing with dementia, and this pathological characteristic is commonly seen in people suffering from Alzheimer's...
Globally around 24 million elderly population are dealing with dementia, and this pathological characteristic is commonly seen in people suffering from Alzheimer's disease (AD). Despite having multiple treatment options that can mitigate AD symptoms, there is an imperative call to advance our understanding of the disease pathogenesis to unfold disease-modifying treatments/therapies. To explore the driving mechanisms of AD development, we stretch out further to study time-dependant changes after Okadaic acid (OKA)-induced AD-like conditions in zebrafish. We evaluated the pharmacodynamics of OKA at two-time points, i.e., after 4-days and 10-days exposure to zebrafish. T-Maze was utilized to observe the learning and cognitive behaviour, and inflammatory gene expressions such as 5-Lox, Gfap, Actin, APP, and Mapt were performed in zebrafish brains. To scoop everything out from the brain tissue, protein profiling was performed using LCMS/MS. Both time course OKA-induced AD models have shown significant memory impairment, as evident from T-Maze. Gene expression studies of both groups have reported an overexpression of 5-Lox, GFAP, Actin, APP, and OKA 10D group has shown remarkable upregulation of Mapt in zebrafish brains. In the case of protein expression, the heatmap suggested an important role of some common proteins identified in both groups, which can be explored further to investigate their mechanism in OKA-induced AD pathology. Presently, the preclinical models available to understand AD-like conditions are not completely understood. Hence, utilizing OKA in the zebrafish model can be of great importance in understanding the pathology of AD progression and as a screening tool for drug discovery.
Topics: Aged; Animals; Humans; Alzheimer Disease; Zebrafish; Proteomics; Actins; Brain; Okadaic Acid; Genomics; Disease Models, Animal
PubMed: 37100105
DOI: 10.1016/j.cbpc.2023.109636 -
Molecules (Basel, Switzerland) Dec 2017In view of the significant neuroprotective effect of , we continued to separate the -butanol and the water extracts from the stems of in order to find the leading...
In view of the significant neuroprotective effect of , we continued to separate the -butanol and the water extracts from the stems of in order to find the leading compounds with significant activity. Two new phenolic glycosides, Clausenolside A-B (-), one new pair of phenolic enantiomers (, ), and two new monoterpenoids, clausenapene A-B (-), together with twelve known analogues (-) were isolated from the stems of . Compounds - were obtained from for the first time. Compounds , , , , and showed strong or moderate potential neuroprotective effects on inhibited PC12 cell injury induced by okadaic acid, and compound exhibited strong potential hepatoprotective activities. Their structures were elucidated on the basis of spectroscopic analyses, including UV, IR, NMR experiments, and electronic circular dichroism (ECD) spectra.
Topics: Animals; Cell Survival; Clausena; Drug Discovery; Drugs, Chinese Herbal; Glycosides; Hep G2 Cells; Humans; Hydrolysis; Monoterpenes; Neuroprotective Agents; PC12 Cells; Phenols; Plant Stems; Rats; Stereoisomerism
PubMed: 29240703
DOI: 10.3390/molecules22122226 -
Toxins May 2023The successful cultivation of Claparède & Lachmann, 1859, isolated from Japanese coastal waters, is presented in this study, which also includes an examination of its...
The successful cultivation of Claparède & Lachmann, 1859, isolated from Japanese coastal waters, is presented in this study, which also includes an examination of its toxin content and production for the first time. Maintaining the strains at a high abundance (>2000 cells per mL) for more than 20 months was achieved by feeding them with the ciliate Lohmann, 1908, along with the addition of the cryptophyte (W.Conrad) D.R.A.Hill, 1992. Toxin production was examined using seven established strains. At the end of the one-month incubation period, the total amounts of pectenotoxin-2 (PTX2) and dinophysistoxin-1 (DTX1) ranged between 132.0 and 375.0 ng per mL (n = 7), and 0.7 and 3.6 ng per mL (n = 3), respectively. Furthermore, only one strain was found to contain a trace level of okadaic acid (OA). Similarly, the cell quota of pectenotoxin-2 (PTX2) and dinophysistoxin-1 (DTX1) ranged from 60.6 to 152.4 pg per cell (n = 7) and 0.5 to 1.2 pg per cell (n = 3), respectively. The results of this study indicate that toxin production in this species is subject to variation depending on the strain. According to the growth experiment, exhibited a long lag phase, as suggested by the slow growth observed during the first 12 days. In the growth experiment, grew very slowly for the first 12 days, suggesting they had a long lag phase. However, after that, they grew exponentially, with a maximum growth rate of 0.56 divisions per day (during Days 24-27), reaching a maximum concentration of 3000 cells per mL at the end of the incubation (Day 36). In the toxin production study, the concentration of DTX1 and PTX2 increased following their vegetative growth, but the toxin production still increased exponentially on Day 36 (1.3 ng per mL and 154.7 ng per mL of DTX1 and PTX2, respectively). The concentration of OA remained below detectable levels (≤0.010 ng per mL) during the 36-day incubation period, with the exception of Day 6. This study presents new information on the toxin production and content of , as well as insights into the maintenance and culturing of this species.
Topics: Marine Toxins; Japan; Bays; Dinoflagellida; Okadaic Acid; Ciliophora
PubMed: 37235353
DOI: 10.3390/toxins15050318