Gian Luigi Mariottini

Mediterranean Jellyfish Venoms: A Review on Scyphomedusae

The production of natural toxins is an interesting aspect, which characterizes the physiology and the ecology of a number of marine species that use them for defence/offence purposes. Cnidarians are of particular concern from this point of view; their venoms are contained in specialized structures–the nematocysts–which, after mechanical or chemical stimulation, inject the venom in the prey or in the attacker. Cnidarian stinging is a serious health problem for humans in the zones where extremely venomous jellyfish or anemones are common, such as in temperate and tropical oceanic waters and particularly along several Pacific coasts, and severe cases of envenomation, including also lethal cases mainly induced by cubomedusae, were reported. On the contrary, in the Mediterranean region the problem of jellyfish stings is quite modest, even though they can have anyhow an impact on public health and be of importance from the ecological and economic point of view owing to the implications on ecosystems and on some human activities such as tourism, bathing and fishing. This paper reviews the knowledge about the various aspects related to the occurrence and the stinging of the Mediterranean scyphozoan jellyfish as well as the activity of their venoms.

The mauve stinger Pelagia noctiluca (Forsskal, 1775). Distribution, ecology, toxicity and epidemiology of stings. A review.

The toxicity of Cnidaria is a subject of concern due to its influence on humans. In particular, jellyfish blooms can highly affect human economical activities, such as bathing, fishery, tourism, etc., as well as the public health. Stinging structures of Cnidaria (nematocysts) produce remarkable effects on human skin, such as erythema, swelling, burning and vesicles, and at times further severe dermonecrotic, cardio- and neurotoxic effects, which are particularly dangerous in sensitive subjects. In several zones the toxicity of jellyfish is a very important health problem, thus it has stimulated the research on these organisms; to date toxicological research on Cnidarian venoms in the Mediterranean region is not well developed due to the weak poisonousness of venoms of jellyfish and anemones living in this area. In spite of this, during last decades several problems were also caused in the Mediterranean by stinging consequent to Cnidarian blooms mainly caused by Pelagia noctiluca (Forsskål, 1775) which is known to be the most venomous Mediterranean jellyfish. This paper reviews the knowledge on this jellyfish species, particularly considering its occurrence and toxicity.

Cytotoxic and Cytolytic Cnidarian Venoms. A Review on Health Implications and Possible Therapeutic Applications

The toxicity of Cnidaria is a subject of concern for its influence on human activities and public health. During the last decades, the mechanisms of cell injury caused by cnidarian venoms have been studied utilizing extracts from several Cnidaria that have been tested in order to evaluate some fundamental parameters, such as the activity on cell survival, functioning and metabolism, and to improve the knowledge about the mechanisms of action of these compounds. In agreement with the modern tendency aimed to avoid the utilization of living animals in the experiments and to substitute them with in vitro systems, established cell lines or primary cultures have been employed to test cnidarian extracts or derivatives. Several cnidarian venoms have been found to have cytotoxic properties and have been also shown to cause hemolytic effects. Some studied substances have been shown to affect tumour cells and microorganisms, so making cnidarian extracts particularly interesting for their possible therapeutic employment. The review aims to emphasize the up-to-date knowledge about this subject taking in consideration the importance of such venoms in human pathology, the health implications and the possible therapeutic application of these natural compounds.

Cytotoxicity of the venom of Pelagia noctiluca forskål (Cnidaria: Scyphozoa)

The activity of Pelagia noctiluca venom was never assessed on cultured cells; therefore, we have evaluated on V79 cells the cytotoxicity, genotoxicity and ATP depletion induced after treatment. Venom did not cause alteration on cell DNA, but showed remarkable cytotoxic properties. With the highest nematocyst concentration (150,000 nematocyst/ml) 74 and 39% cells survived after 1 and 3 h, respectively, when evaluated by Trypan blue. Treated cells showed increased ATP levels during the same time. Preliminary HPLC analyses have showed the occurrence of a protein containing peak.

In vitro evaluation of the cytotoxic, hemolytic and clastogenic activities of Rhizostoma pulmo toxin(s)

Cytotoxic, hemolytic and clastogenic activities of Rhizostoma pulmo toxin(s) contained in the jelly tissue free of nematocysts were investigated in mammalian cells with in vitro procedures. At the concentration of 37.6 microg/ml the tissue protein produced the death of 50% V79 cells; a similar potency was observed in terms of hemolytic activity. The toxin(s) was not clastogenic for human lymphocytes in culture at the concentration of 5 microg/ml.

Toxicity of jellyfish and sea-anemone venoms on cultured V79 cells

Cnidarian toxins exert an influence on human activities and public health. The cytotoxicity of crude toxins (nematocyst and surrounding tissue venom) of Aequorea aequorea, Rhizostoma pulmo and Anemonia sulcata was assessed on V79 cells. Rhizostoma pulmo and Anemonia sulcata crude venoms showed remarkable cytotoxicity and killed all treated cells at highest tested concentration within 2 and 3 hr, respectively. Aequorea aequorea crude venom greatly affected growth rate during long-term experiments. No genotoxic effect was observed.

The role of Cnidaria in drug discovery. A review on CNS implications and new perspectives.

Many organisms produce bioactive substances used in the production of drugs. In this context, Cnidaria occupy a major position; for this reason, research on new bioactive substances has focused upon them as an interesting target. As a matter of fact, substances and extracts able to fight human diseases have been found in cnidarians, several of which have been studied in laboratories using animal models or cell cultures and, at present, some are in the pre-clinical phase. This review aims to highlight the research on existing drugs or new drug candidates extracted from Cnidaria and the recent patents published in this field; furthermore, as many cnidarian venoms are known to have an impact on the CNS and on neuromuscular transmission, this review particularly considers the research concerning CNS drug discovery and pending patents.

Assessment of the Antimicrobial Activity of Algae Extracts on Bacteria Responsible of External Otitis.

External otitis is a diffuse inflammation around the external auditory canal and auricle, which is often occurred by microbial infection. This disease is generally treated using antibiotics, but the frequent occurrence of antibiotic resistance requires the development of new antibiotic agents. In this context, unexplored bioactive natural candidates could be a chance for the production of targeted drugs provided with antimicrobial activity. In this paper, microbial pathogens were isolated from patients with external otitis using ear swabs for over one year, and the antimicrobial activity of the two methanol extracts from selected marine (Dunaliella salina) and freshwater (Pseudokirchneriella subcapitata) microalgae was tested on the isolated pathogens. Totally, 114 bacterial and 11 fungal strains were isolated, of which Staphylococcus spp. (28.8%) and Pseudomonas aeruginosa (P. aeruginosa) (24.8%) were the major pathogens. Only three Staphylococcus aureus (S. aureus) strains and 11 coagulase-negative Staphylococci showed resistance to methicillin. The two algal extracts showed interesting antimicrobial properties, which mostly inhibited the growth of isolated S. aureus, P. aeruginosa, Escherichia coli, and Klebsiella spp. with MICs range of 1.4 × 109 to 2.2 × 1010 cells/mL. These results suggest that the two algae have potential as resources for the development of antimicrobial agents.

A fast centrifuge method for nematocyst isolation from Pelagia noctiluca Forskal (Cnidaria: Scyphozoa)

Nematocyst isolation from surrounding tissue is an important step to characterize Cnidarian venom. Although several protocols have been used to extract venoms from cnidarian tissues, the complete isolation of nematocysts from tissue is still difficult. The goal of the present work was to evaluate the effectiveness of three different media, Percoll, Ficoll and Methylcellulose in isolating nematocysts from Pelagia noctiluca tentacles by centrifugation. The complete sedimentation of nematocysts and tissue fragments to the bottom of the test tubes was observed in Ficoll and Methylcellulose suspensions. The best result was obtained using a discontinuous density gradient of Percoll: three types of nematocysts were concentrated in three different fractions along the density gradient. Protein assay and preliminary chromatographic analyses confirmed these results.

Neurotoxic and Neuroactive Compounds from Cnidaria: Five Decades of Research….and More

Cnidarians are numbered among the most venomous organisms. Their venoms are contained in intracellular capsules, nematocysts, which inject the content into preys/attackers through an eversion system resembling a syringe needle. Several cnidarian venoms have activity against the nervous system, being neurotoxic, or affect other systems whose functioning is under nerve control. Besides direct damage to nerve cells, the activity on ionic conductance, blockade of neuromuscular junctions, and influence on action potentials and on voltage-gated channels have been described. Therefore, cnidarians can be a useful source of nervous system-targeted compounds which could have, in perspective, a role in the therapy of some nervous system diseases. Following this idea, this article aims to review the existing data about the neuroactive properties of cnidarian venoms and their possible usefulness in tackling some neurological diseases as well as neurodegenerative age-related diseases whose incidence is expected to raise in the next decades owing to the increase of life expectancy.