The venom and the toxicity of Pelagia noctiluca (Cnidaria: Scyphozoa). A review of three decades of research in Italian laboratories and future perspectives

Recurrent outbreaks of Pelagia noctiluca and health problems consequent to stings were recorded during the last decades. This phenomenon forced some Italian University laboratories to study this cnidarian. The first studies concerned the distribution, biochemical composition and morphology of nematocysts of Pelagia noctiluca. The discharge mechanism of nematocysts was defined starting from early 1980s when enzymes, cations, anions, and pH were observed to have an influence on this process. Notably, trypsin, extreme pH values, some anions (I–, Cl–, SCN–), and thioglycolate were seen to induce, while La3+ and Gd3+ to prevent, nematocyst discharge. The discharge of both in situ and isolated nematocyst was found to be Ca2+ dependent. Furthermore, Pelagia noctiluca nematocysts were seen to retain their discharging capacity in distilled water. The toxicological evaluations were carried out mainly using the crude venom from Pelagia noctiluca because, unfortunately, to date the composition of venom remains unknown. Hemolytic and cytotoxic properties of crude venom have been evaluated on erythrocytes and cultured guinea-pig fibroblasts, mouse fibroblasts, and cancer (neuroblastoma) cells. The activity of Pelagia noctiluca venom on other cnidarians has been also assessed. The crude venom induced apoptosis by reactive oxygen species generation and decrease in mitochondrial transmembrane potential, loss of mitochondrial integrity, and alteration of cell membrane permeability. A pore-forming action mechanism on mitochondrial membrane with oxidative damage was also suggested. The protective activity of some compounds against envenomations has been also evaluated. Future challenges will concern the attempts to characterize the venom and to perform a wider screening of cytotoxicity induced to normal and cancer cells

Evidence for aquaporin-mediated water transport in nematocytes of the jellyfish Pelagia noctiluca.

Nematocytes, the stinging cells of Cnidarians, have a cytoplasm confined to a thin rim. The main cell body is occupied by an organoid, the nematocyst, containing the stinging tubule and venom. Exposed to hypotonic shock, nematocytes initially swell during an osmotic phase (OP) and then undergo regulatory volume decrease (RVD) driven by K+, Cl- and obligatory water extrusion mechanisms. The purpose of this report is to characterize the OP. Nematocytes were isolated by the NaSCN/Ca2+ method from tentacles of the jellyfish Pelagia noctiluca, collected in the Strait of Messina, Italy. Isolated nematocytes were subjected to hyposmotic shock in 65% artificial seawater (ASW) for 15 min. The selective aquaporin water channel inhibitor HgCl2 (0.1-25 µM) applied prior to osmotic shock prevented the OP and thus RVD. These effects were attenuated in the presence of 1mM dithiothreitol (DTT), a mercaptide bond reducing agent. AgNO3 (1 µM) and TEA (tetraethylammonium, 100 µM), also reported to inhibit water transport, did not alter the OP but significantly diminished RVD, suggesting different modes of action for the inhibitors tested. Based on estimates of the nematocyte surface area and volume, and OP duration, a relative water permeability of ∼10-7 cm/sec was calculated and the number of putative aquaporin molecules mediating the OP was estimated. This water permeability is 3-4 orders of magnitude lower in comparison to higher order animals and may constitute an evolutionary advantage for Cnidarian survival

Mechanisms of hyposmotic volume regulation in isolated nematocytes of the anthozoan Aiptasia diaphana.

The nature and role of potassium (K) and water transport mediating hyposmotically-induced regulatory volume decrease (RVD) were studied in nematocytes dissociated with 605 mM thiocyanate from aconti

Effect of cadmium on anion exchange capability through Band 3 protein in human erythrocytes

The efficiency of Band 3 protein, mediating HCO3-/Cl- exchange across erythrocytes membrane, is reduced by oxidative stress. The aim of the present study was to verify whether Band 3 protein efficiency is compromised by treatment with Cadmium (Cd2+), an extremely toxic heavy metal known to interfere with antioxidant enzymes, energy metabolism, gene expression and cell membranes. To this end, the rate constant for SO4= uptake through Band 3 protein (accounting for velocity of anion exchange) was measured along with membrane –SH groups, Malonyldialdehyde (MDA) and Band 3 protein expression levels in Cd2+ -treated human erythrocytes (300 µM, 1 mM). Our results show that Cd2+ reduced the rate constant for SO4= uptake, with a significant increase in MDA levels at both concentrations and with a reduction in –SH groups observed after 1 mM Cd2+ treatment, whereas Band 3 protein expression levels were unchanged in both conditions. In conclusion: i) Cd2+ reduces Band 3 protein efficiency via different mechanisms depending on metal concentration and with unchanged expression levels; ii) the assessment of Band 3 protein anion exchange capability is a good tool to assay the impact of heavy metals on cell homeostasis and, possibly, useful for diagnosis and monitoring of devalopment of Cd2+ toxicity-related pathologies

Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice

<p>Abstract</p> <p>Background</p> <p>Extracts of <it>Hypericum perforatum </it>(St. John's wort) have been traditionally recommended for a wide range of medical conditions, in particular mild-to-moderate depression. The present study was designed to investigate the effect of Hypericum perforatum treatment in a mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone administration.</p> <p>Methods</p> <p>CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF), Novelty-Suppressed Feeding (NSF), Forced Swim Test (FST) were performed. Cell proliferation in hippocampal dentate gyrus (DG) was investigated by both 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgi-impregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg) has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined.</p> <p>Results</p> <p>The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration.</p> <p>Conclusion</p> <p>These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment.</p

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

Cytotoxicity of venom from heterotrichous microbasic eurytele nematocysts of Pelagia noctiluca (Cnidaria: Scyphozoa) to L929 mouse lung fibroblasts. Preliminary results.

During last decades many studies highlighted cnidarian relevance in worldwide trophic chains, as well as the considerable frequency and size of outbreaks over the years. A high inter-specific variability, survival ability and harsh conditions resistance built a clear path for these animals to the top of trophic chains, with a corresponding raising impact on sea-related anthropogenic activities. Indeed, cnidarians possess efficient stinging characteristics and represent a threat to bathers and fishermen. Pelagia noctiluca (Forssk\ue5l, 1775), the \u201cMauve Stinger\u201d, is a common Mediterranean scyphozoan jellyfish. It occurs mainly from March to May, but also throughout the year in South Tyrrhenian waters around Northeastern Sicily. The venomousness of this jellyfish is due to three main different kinds of nematocysts, which are known to contain toxins which at present are not exhaustively known. In this study, a first evaluation of the cytotoxic activity of heterotrichous microbasic eurytele nematocysts from Pelagia noctiluca is presented and discussed. Nematocysts were isolated from tentacles of Pelagia noctiluca and the content was extracted by sonication (aqueous extract). Cytotoxicity assays employing MTT assay and Trypan Blue dye exclusion were carried out on L929 mouse lung fibroblasts. Aqueous extracts induced cytotoxicity to L929 cells with 36.9% cell survival after 24 hours treatment with aqueous extract of 150 7103 P.noctiluca nematocysts/ml, and 68.9% cell survival after treatment with extract of 75 7103 nematocysts/ml. Further analysis, including the evaluation of the oxidative stress and considering cellular targets such as apoptotic ways, antioxidant enzymes, ion channel inhibition, ROS production, and cellular signals correlated to protein expression could be further research developments and are thought to be required in order to understand the suitability of extracts from Pelagia noctiluca nematocysts as valuables biopharmaceutical substances

Biological activity of extract from Styela plicata and Ascidia mentula (Ascidiacea)

The biological activity of extract obtained from the ascidians Styela plicata and Ascidia mentula, living in the coastal lake Faro (Messina, Italy) was ascertained with specific regard to cytotoxic effect, tested on cultured human embryonic kidney (HEK 293 Phoenix) cells after 12, 24 or 48 h, and to antimicrobial effect (10 mg/mL), assayed on both Gram positive and negative strains. Nitrosative stress, possibly induced by the extract on HEK 293 cells and assessed by NO2 –/NO3 – production measurement, was also verified. With regard to cytotoxic activity, A. mentula extract was more effective than S. plicata one, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, with toxic action due to nitrosative stress. S. plicata extract had a more significant antimicrobial activity than A. mentula. The present findings provide a first evidence of the biological power exhibited by both S. plicata and A. mentula extracts, thus increasing the knowledge about the biological activity of marine compounds and providing novel information to possibly correlate the different toxicity pattern displayed by both specimens and their distribution in the lake Faro (Messina)