| 1. |
- Jolkkonen, Mikael, et al.
(författare)
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Kinetic evidence for different mechanisms of interaction of black mamba toxins MT alpha and MT beta with muscarinic receptors
- 2001
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Ingår i: Toxicon. - 0041-0101 .- 1879-3150. ; 39:2-3, s. 377-382
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Tidskriftsartikel (refereegranskat)abstract
- By studying the influence of two toxins from the black mamba Dendroaspis polylepis on the kinetics of [H-3]-N-methylscopolamine binding to muscarinic acetylcholine receptors from rat cerebral cortex, it was revealed that these toxins, MT alpha and MT beta, interact with the receptors via kinetically distinct mechanisms. MT beta bound to receptors in a one-step, readily reversible process with the dissociation constant K-d = 5.3 mu M. The binding mechanism of MT alpha was more complex, involving at least two consecutive steps. A fast receptor-toxin complex formation (K-T = 3.8 mu M) was followed by a slow process of isomerisation of this complex (k(i) = 1.8 x 10(-2) s(-1), half-time 39 s). A similar two-step interaction mechanism has been established for a related toxin, MT2 from the green mamba D. angusticeps (K-T = 1.4 mu M, k(i) = 8.3 x 10(-4) s(-1), half-time 840 s). The slow isomerisation process delays the effect of MT alpha and MT2, but increases their apparent potency compared to toxins unable to induce the isomerisation process.
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| 2. |
- Sundell, I.B., et al.
(författare)
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In vitro procoagulant and anticoagulant properties of Naja naja naja venom
- 2003
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Ingår i: Toxicon. - 0041-0101 .- 1879-3150. ; 42:3, s. 239-247
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Tidskriftsartikel (refereegranskat)abstract
- Bites by the Indian cobra (Naja naja naja) are common in India and Sri Lanka because of its close association with humans. Cobra venoms are complex and contain several toxic components, including neurotoxins that cause post-synaptic neuromuscular blockade with respiratory paralysis and even death. Bites may also cause extensive local necrosis by mechanisms not fully elucidated. Although no significant coagulopathy has been reported, N.n. naja venom can form blood clots in vitro by activating prothrombin as demonstrated by thrombin-specific chromogenic substrate. Scanning electron microscopy demonstrates that the clots formed by venom lack the thin fibrin strands of normal blood clots formed by thromboplastin or glass contact. Rheometry shows that clots formed by venom have abnormally low elasticity over an extended period and then, as the platelets contract, a retarded and more feeble increase in elasticity. Purified N.n. naja venom PLA2 inhibits platelet aggregation in PRP and explains the decreased clot retraction and retarded and compromised elasticity build up. The present study shows that the PLA 2 and the prothrombin activator from N.n. naja venom have effects on haemostasis and blood clotting, although such effects are not observed systemically in envenomed humans. © 2003 Elsevier Ltd. All rights reserved.
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| 4. |
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| 5. |
- Lundqvist, Johan, et al.
(författare)
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Microcystins activate nuclear factor erythroid 2-related factor 2 (Nrf2) in human liver cells in vitro - Implications for an oxidative stress induction by microcystins
- 2017
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 126, s. 47-50
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Tidskriftsartikel (refereegranskat)abstract
- Microcystins, a potential threat to drinking water quality, are hepatotoxic but it has remained unclear if microcystins induce oxidative stress. We investigated if four microcystins could activate the Nrf2 pathway, a regulator of oxidative stress response. Nrf2 activity was significantly increased by microcystin-LR and-RR at 10 mu M, by microcystin-LY at 3 mu M, by [D-Asp3]-LR and by microcystin-LR at 1 mu M. Our results lend support to the suggestion that microcystins may induce oxidative stress response. (C) 2016 Elsevier Ltd. All rights reserved.
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| 6. |
- Malina, Tamás, et al.
(författare)
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Individual variability of venom from the European adder (Vipera berus berus) from one locality in Eastern Hungary
- 2017
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 135, s. 59-70
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Tidskriftsartikel (refereegranskat)abstract
- We have revealed intra-population variability among venom samples from several individual European adders (Vipera berus berus) within a defined population in Eastern Hungary. Individual differences in venom pattern were noticed, both gender-specific and age-related, by one-dimensional electrophoresis. Gelatin zymography demonstrated that these individual venoms have different degradation profiles indicating varying protease activity in the specimens from adders of different ages and genders. Some specimens shared a conserved region of substrate degradation, while others had lower or extremely low protease activity. Phospholipase A(2) activity of venoms was similar but not identical. Interspecimen diversity of the venom phospholipase A(2)-spectra (based on the components' molecular masses) was detected by MALDI-TOF MS. The lethal toxicity of venoms (LD50) also showed differences among individual snakes. Extracted venom samples had varying neuromuscular paralysing effect on chick biventer cervicis nerve-muscle preparations. The paralysing effect of venom was lost when calcium in the physiological salt solution was replaced by strontium; indicating that the block of twitch responses to nerve stimulation is associated with the activity of a phospholipase-dependent neurotoxin. In contrast to the studied V.b. berus venoms from different geographical regions so far, this is the first V.b berus population discovered to have predominantly neurotoxic neuromuscular activity. The relevance of varying venom yields is also discussed. This study demonstrates that individual venom variation among V.b. berus living in particular area of Eastern Hungary might contribute to a wider range of clinical manifestations of V.b. hems envenoming than elsewhere in Europe.
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| 7. |
- Persson, Karl-Johan, et al.
(författare)
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Differential tolerance to cyanobacterial exposure between geographically distinct populations of Perca fluviatilis
- 2013
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Ingår i: Toxicon. - : Elsevier. - 0041-0101 .- 1879-3150. ; :76, s. 178-186
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Tidskriftsartikel (refereegranskat)abstract
- Toxic cyanobacterial blooms are an important problem worldwide. Cyanobacteria may negatively impact young-of-the-year (YOY) fish directly (toxin production, turbidity, decrease in water quality) or indirectly (trophic toxin transfer, changes in prey species composition). Here we test whether there are any differences in cyanobacterial tolerance between four geographically distinct populations of European perch (Perca fluviatilis). We show that P. fluviatilis may develop tolerance against cyanobacteria demonstrated by the ability of individuals from a marine site (exposed to annual cyanobacterial blooms) to increase their detoxification more than individuals from an oligotrophic site (rarely exposed to cyanobacteria). Our results also revealed significant interaction effects between genotypes within a population and response to cyanobacterial exposure in terms of absolute growth and detoxification activity. This genotype by treatment interaction may result in local adaptations to cyanobacterial exposure in P. fluviatilis. Hence, the sensitivity against cyanobacterial exposure may differ between within species populations increasing the importance of local management of fish populations.
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| 8. |
- Persson, Karl-Johan, et al.
(författare)
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Effects of the filamentous cyanobacterium Nodularia on fitness and feeding behavior of young-of-the-year (YOY) Eurasian perch (Perca fluviatilis)
- 2011
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 57:7-8, s. 1033-1040
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Tidskriftsartikel (refereegranskat)abstract
- AbstractThis study reveals that both cyanobacterial toxicity and turbidity have the potential to reduce the growth and energy storage of young-of-the-year (YOY) perch and thereby influence survival rates. During the 1990's a reduction in recruitment of YOY perch (Perca fluviatilis) occurred along the Swedish East coast. Concurrently, large blooms of filamentous cyanobacteria have increased in the Baltic Proper and in coastal waters. This study examined whether extended exposure to toxic and non-toxic filamentous cyanobacterium Nodularia affect YOY perch growth and feeding behavior under simulated bloom conditions (30 days at 50 μg Chl a L−1). Specific growth rate (SGR), the somatic condition index (SCI) and the lipid content of YOY perch (10–12 weeks old) were significantly lower in perch exposed to Nodularia compared to fed controls (no Nodularia). YOY perch exposed to non-toxic Nodularia displayed a higher attack rate than perch living in Nodularia free controls in 2 out of 3 trials. Reductions in growth and energy storage, mediated by cyanobacteria, increase the risk of starvation and predation and could locally influence recruitment of YOY perch.Highlights► We investigate the effects of toxic and non-toxic cyanobacterial (Nodularia sp.) on young-of-the-year (YOY) perch (Perca fluviatilis). ► Endpoints are specific growth rate (SGR), lipid content and feeding behavior (feeding and attack rate). ► Results show that both non-toxic and toxic Nodularia reduce SGR and lipid content of YOY perch. ► Reduced growth and energy storage may locally influence recruitment of YOY perch.
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| 9. |
- Rosén, Johan, et al.
(författare)
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A new method for analysis of underivatized free beta-methylamino-alanine : Validation and method comparison
- 2016
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 121, s. 105-108
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Tidskriftsartikel (refereegranskat)abstract
- A new method was developed for analysis of free beta-Methylamino-alanine (BMAA) in biological matrices. The method is based on direct analysis of the underivatized molecule, using an amide column for separation by Hydrophilic Interaction Liquid Chromatography (HILIC) and detection by tandem mass spectrometry (MS/MS) using a deuterium labeled internal standard. The use of Ultra-High Performance Liquid Chromatography (UHPLC) combined with MS/MS detection allowed for high chromatographic resolution and a low limit of detection (0.025 mu g/g wet weight (ww) in mussels). The method was validated by analyzing spiked blank mussels from the Baltic Sea (0.15-4.4 mu g/g (ww), trueness 99%-105%, RSD 2%-8%). An inter-laboratory comparative analysis of extracts of mussel was performed. The mussels were extracted according to an established protocol for analysis of free BMAA, and the extracts were then analyzed in parallel by the new method and a validated procedure based on detection of BMAA derivatized with dansyl chloride. Both methods detected BMAA in similar concentrations. Thus, derivatization with dansyl chloride did not influence the results compared to direct detection. The new method presents an alternative to the commonly applied derivatization step, and is proved through validation and method comparison to reliably identify and quantify free BMAA at low concentration levels.
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| 10. |
- Sousa, Maria Ligia, et al.
(författare)
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Portoamides A and B are mitochondrial toxins and induce cytotoxicity on the proliferative cell layer of in vitro microtumours
- 2020
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Ingår i: Toxicon. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0041-0101 .- 1879-3150. ; 175, s. 49-56
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Tidskriftsartikel (refereegranskat)abstract
- Cyanobacteria are known to produce many toxins and other secondary metabolites. The study of their specific mode of action may reveal the biotechnological potential of such compounds. Portoamides A and B (PAB) are cyclic peptides isolated from the cyanobacteria Phormidium sp. due to their growth repression effect on microalgae and were shown to be cytotoxic against certain cancer cell lines. In the present work, viability was assessed on HCT116 colon cancer cells grown as monolayer culture and as multicellular spheroids (MTS), non-carcinogenic cells and on zebrafish larvae. HCT116 cells and epithelial RPE-1(hTERT) cells showed very similar degrees of sensitivities to PAB. PAB were able to penetrate the MTS, showing a four-fold high IC50 compared to monolayer cultures. The toxicity of PAB was similar at 4 degrees C and 37 degrees C suggesting energy-independent uptake. PAB exposure decreased ATP production, mitochondrial maximal respiration rates and induced mitochondrial membrane hyperpolarization. PAB induced general organelle stress response, indicated by an increase of the mitochondrial damage sensor PINK-1, and of phosphorylation of eIF2 alpha, characteristic for endoplasmic reticulum stress. In summary, these findings show general toxicity of PAB on immortalized cells, cancer cells and zebrafish embryos, likely due to mitochondrial toxicity.
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