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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.
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