Abstract
BackgroundPreviously, we have reported that most, if not all, of the Scyphozoan jellyfish venoms contain multiple components of metalloproteinases, which apparently linked to the venom toxicity. Further, it is also well known that there is a positive correlation between the inflammatory reaction of dermal tissues and their tissue metalloproteinase activity. Based on these, the use of metalloproteinase inhibitors appears to be a promising therapeutic alternative for the treatment of jellyfish envenomation.Methodology and Principal FindingsTetracycline (a metalloproteinase inhibitor) has been examined for its activity to reduce or prevent the dermal toxicity induced by Nemopilema nomurai (Scyphozoa: Rhizostomeae) jellyfish venom (NnV) using in vitro and in vivo models. HaCaT (human keratinocyte) and NIH3T3 (mouse fibroblast) incubated with NnV showed decreases in cell viability, which is associated with the inductions of metalloproteinase-2 and -9. This result suggests that the use of metalloproteinase inhibitors, such as tetracycline, may prevent the jellyfish venom-mediated local tissue damage. In vivo experiments showed that comparing with NnV-alone treatment, tetracycline pre-mixed NnV demonstrated a significantly reduced progression of dermal toxicity upon the inoculation onto rabbit skin.Conclusions/SignificanceIt is believed that there has been no previous report on the therapeutic agent of synthetic chemical origin for the treatment of jellyfish venom-induced dermonecrosis based on understanding its mechanism of action except the use of antivenom treatment. Furthermore, the current study, for the first time, has proposed a novel mechanism-based therapeutic intervention for skin damages caused by jellyfish stings.
Highlights
Over the last decade, unusual large blooms of N. nomurai jellyfish have occurred in Yellow sea, East China Sea, and East Sea [1] and the patients stung by this jellyfish species have increased correspondingly
We examined the ability of tetracycline to inhibit the clinical sequela of N. nomurai jellyfish envenomation
Nomurai Jellyfish Venom In order to estimate the toxic effects of N. nomurai jellyfish venom (NnV), HaCaT and NIH3T3 cells were incubated for 24 h with increasing concentrations of NnV
Summary
Unusual large blooms of N. nomurai jellyfish have occurred in Yellow sea, East China Sea, and East Sea [1] and the patients stung by this jellyfish species have increased correspondingly. It has been reported that over 2000 cases of N. nomurai jellyfish envenomation occurred in the coastal areas of Korea, Japan and China since 1983, including fatal cases in some patients with the jellyfish sting [2]. We have shown that most, if not all, of the Scyphozoan jellyfish venoms contain multiple components of various metalloproteinases, which largely contribute to their cytotoxic activities. All the Scyphozoan jellyfish venoms examined showed gelatinolytic, caseinolytic, and fibrinolytic activities, each of which contains a multitude of enzyme components with molecular weights between 17 and 130 kDa [7]. We have reported that most, if not all, of the Scyphozoan jellyfish venoms contain multiple components of metalloproteinases, which apparently linked to the venom toxicity. The use of metalloproteinase inhibitors appears to be a promising therapeutic alternative for the treatment of jellyfish envenomation
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