Protective effects of batimastat against hemorrhagic injuries in delayed jellyfish envenomation syndrome models.

Abstract

Previously, we established delayed jellyfish envenomation syndrome (DJES) models and proposed that the hemorrhagic toxins in jellyfish tentacle extracts (TE) play a significant role in the liver and kidney injuries of the experimental model. Further, we also demonstrated that metalloproteinases are the central toxic components of the jellyfish Cyanea capillata (C. capillata), which may be responsible for the hemorrhagic effects. Thus, metalloproteinase inhibitors appear to be a promising therapeutic alternative for the treatment of hemorrhagic injuries in DJES. In this study, we examined the metalloproteinase activity of TE from the jellyfish C. capillata using zymography analyses. Our results confirmed that TE possessed a metalloproteinase activity, which was also sensitive to heat. Then, we tested the effect of metalloproteinase inhibitor batimastat (BB-94) on TE-induced hemorrhagic injuries in DJES models. Firstly, using SR-based X-ray microangiography, we found that BB-94 significantly improved TE-induced hepatic and renal microvasculature alterations in DJES mouse model. Secondly, under synchrotron radiation micro-computed tomography (SR-μCT), we also confirmed that BB-94 reduced TE-induced hepatic and renal microvasculature changes in DJES rat model. In addition, being consistent with the imaging results, histopathological and terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL)-like staining observations also clearly corroborated this hypothesis, as BB-94 was highly effective in neutralizing TE-induced extensive hemorrhage and necrosis in DJES rat model. Although it may require further clinical studies in the near future, the current study opens up the possibilities for the use of the metalloproteinase inhibitor, BB-94, in the treatment of multiple organ hemorrhagic injuries in DJES.

• Authors: Beilei Wang, Dan Liu, Guoyan Liu, Xin Zhang, Qianqian Wang, Jiemin Zheng, Yonghong Zhou, Qian He, Liming Zhang
• Journal: Toxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 108 Pg. 232-9 (Dec 15 2015) ISSN: 1879-3150 [Electronic] England
• PMID: 26546696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Cnidarian Venoms
• Protective Agents
• Thiophenes
• Phenylalanine
• batimastat
• Metalloproteases

Topics

• Angiography
• Animals
• Bites and Stings (drug therapy)
• Cnidarian Venoms (toxicity)
• Hemorrhage (prevention & control)
• In Situ Nick-End Labeling
• Kidney (drug effects, pathology)
• Liver (drug effects, pathology)
• Male
• Metalloproteases (antagonists & inhibitors, chemistry, toxicity)
• Mice
• Necrosis (prevention & control)
• Phenylalanine (analogs & derivatives, therapeutic use)
• Protective Agents (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Scyphozoa
• Syndrome
• Thiophenes (therapeutic use)
• X-Ray Microtomography