Abstract
Jellyfish stingings are currently raising serious public health concerns around the world. Hence, the search for an effective first aid reagent for the envenomation has been the goal of many investigators in the field. There have been a few previous reports of in vivo as well as in vivo studies suggesting the metalloproteinase activity of scyphozoan jellyfish venom, such as N. nomurai venom (NnV), plays a major role in the pathogenesis. These results have inspired us to develop a metalloproteinase inhibitor as a candidate for the treatment of Scyphozoan jellyfish envenomation. It has been previously demonstrated that the major polyphenol component in green tea, epigallocatechin-3-gallate (EGCG), can inhibit metalloproteinase activity of snake venoms. In fact, plant polyphenols as potential therapeutics have been shown to exert positive effects on neutralizing snake venoms and toxins. In the present study, we found that EGCG significantly inhibits the toxic proteases of NnV in a concentration-dependent manner. Human keratinocyte (HaCaT) and Human dermal fibroblast (HDF) cell culture studies showed that EGCG treatment can protect the cells from NnV-induced cytotoxicity which has been accompanied by the down-regulation of human matrix metalloproteinase (MMP)-2 and -9. Simulated rat NnV envenomation study disclosed that topical treatments with EGCG considerably ameliorated the progression of the dermonecrotic lesions caused by NnV. EGCG also reduced the activitions of tissue MMP-2 and MMP-9, which seem to be crucial players in the dermal toxic responses induced by NnV. Therefore, we propose that EGCG might be an effective therapeutic agent for the treatment of cutaneoous jellyfish symptoms.
Highlights
Jellyfish envenomation has been a public health problem for a long time in all over the world, especially for Australia and tropical part in Southeast A sia[1,2,3,4,5]
To verify if EGCG can modulate the metalloproteinases of N. nomurai venom (NnV), gelatin zymography has been performed (Fig. 1A)
As shown by the white bands in zymography, NnV alone showed prominent gelatinolytic activity, which was almost completely suppressed in the presence of EGCG in a concentration-dependent manner
Summary
Jellyfish envenomation has been a public health problem for a long time in all over the world, especially for Australia and tropical part in Southeast A sia[1,2,3,4,5]. The use of vinegar (or 4% acetic acid) is commonly accepted as a first aid in the world for jellyfish stinging It can stimulate nematocyst discharge in some jellyfish species, aggravating the complications, especially for Scyphozoa. According to our previous study, the treatment of 4% acetic acid against Scyphozoan N. nomurai jellyfish tentacles surprisingly caused massive nematocyst discharges, whereas Cubozoan Carybdea brevipedalia did not[12]. We have investigated a novel therapeutic reagent which can neutralize and prevent the local tissue injuries caused by scyphozoan N. nomurai jellyfish venom. The inhibition of toxic metalloproteinases in jellyfish venom may protect the local tissue damages, and increase the survival rate of the victim by suppressing the systemic effect of the venoms. We have investigated the potential therapeutic/preventive effects of EGCG on NnV-induced dermal toxicity using in vitro and in vivo models
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