Protective effects of batimastat against hemorrhagic injuries in delayed jellyfish envenomation syndrome models. (15th December 2015)

• Record Type: Journal Article
• Authors: Wang, Beilei; Liu, Dan; Liu, Guoyan; Zhang, Xin; Wang, Qianqian; Zheng, Jiemin; Zhou, Yonghong; He, Qian; Zhang, Liming
• Is Part Of: Toxicon. Volume 108(2015)
• Page Start: 232
• Page End: 239
• Publication Date: 2015-12-15
• Subjects: Jellyfish -- Cyanea capillata -- Delayed jellyfish envenomation syndrome -- Metalloproteinase -- Batimastat; AJES acute jellyfish envenomation syndrome -- SD Sprague-Dawley -- PBS phosphate buffered saline -- PMH 10-phenanthroline monohydrate -- SSRF Shanghai Synchrotron Radiation Facility -- MMPs matrix metalloproteinases -- ECM extracellular matrix -- SVMPs snake venom metalloproteinases -- MMPI MMP inhibitor; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2015.10.022
• Languages: English
• ISSNs: 0041-0101

Abstract

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. Highlights: Establishment of delayed DJES models proposed the role of TE in hemorrhagic injuries. Metalloproteinases are responsible for the hemorrhagic effects of TE. Batimastat protected the TE-induced hemorrhagic injuries in DJES models.