Detection of microvasculature alterations by synchrotron radiation in murine with delayed jellyfish envenomation syndrome
Introduction
Over the past decade, a massive outbreak of jellyfish has been taking place in worldwide sea areas, including the German Bight (Greve, 1994), the southeast Florida coast (Radwan et al., 2001), the northern tropical waters of Australia (Winter et al., 2010) and the east Asian coast (Kima et al., 2006), which has caused severe economic damages to fishery industries (Dong et al., 2010, Jiang et al., 2008). In addition, jellyfish sting can be dangerous to both fishermen and swimmers (Lee et al., 2011). It has been reported that venomous jellyfish can result in severe local and systemic diseases, and even deaths in some cases (Burnett, 2001, Cegolon et al., 2013, Lippmann et al., 2011).
The scyphozoan Cyanea capillata is widely distributed in Chinese coastal areas (Dong et al., 2010, Wang et al., 2012) and is well-known to humans due to their stinging effects (Kristenson, 1949, Lassen et al., 2011). Humans can respond with cutaneous irritations, pain, and even with cardiopulmonary failure after accidental contact with Cyanea sp. (Kristenson, 1949, Tibballs, 2006). Using the tentacle extract (TE) from the jellyfish C. capillata, we have also systematically evaluated the toxicity of the jellyfish venom in rats. Deaths within 2 h could be attributed to acute heart- or nerve-related toxicities after venom administration, while deaths between 2 and 48 h might be involved multiple organ injuries. Compared with the acute death within 2 h, we defined the multiple organ injuries, developed 2 h later, as the delayed jellyfish envenomation syndrome (DJES), which deserves more attention because the patients with DJES have a relatively wide time window to get clinical treatment (Wang et al., 2013a). Although the precise mechanism of DJES is not clear, previous reports from our laboratory have demonstrated that TE could induce hemorrhagic necrosis in vital organs such as lung, liver and kidney. Besides, according to some recent reports (Kang et al., 2013, Lee et al., 2011), jellyfish may contain some proteolytic enzymes that can cause hemorrhagic effect via the degradation of extracellular matrix and connective tissue surrounding blood vessels. We speculated that TE might also contain such proteases that disrupted the integrity of microvasculars, resulting in hemorrhage and injury of the vital organs and finally causing or aggravating multiple organ dysfunctions in DJES. Thus, visualizing the microvascular network is an important step to understand the mechanism of DJES and develop effective intervention strategies.
Current studies on vessel morphometry were mainly based on light microscopy (Abdul-Karim et al., 2003, Mizutani and Suzuki, 2012). However, it has some significant limitations. For example, it can only be used for sectioned samples because the absorbance and refraction of the visible light interfere with the internal structures of biological objects and this interference increases with tissue thickness (Mizutani and Suzuki, 2012). In addition, current microscopic methods still fail to reveal the whole microvascular network of the specimen due to the restricted field of view (Plouraboue et al., 2004). By contrast, X-rays have a great advantage over traditional microscopic methods in that it can pass through biological tissues more easily with less refraction (Mizutani and Suzuki, 2012). Therefore, nowadays X-ray angiographic techniques are widely used in clinical practice. However, conventional angiography is still not suitable for animal microangiographic studies due to the limited resolution (Liu et al., 2010, Lu et al., 2010, Mori et al., 1996). Fortunately, recent reports show that the newly developed techniques, the synchrotron radiation (SR) -based X-ray microangiography and micro-computed tomography (μCT), with a high-resolution and high-speed imaging system, are allowing us to obtain high-resolution images of the microcirculation in small animals (Iwasaki et al., 2007, Kobayashi et al., 2004, Liu et al., 2010).
Therefore, in the present study, we firstly combined the microangiography and μCT techniques to investigate whether TE could induce microvasculature alterations in vivo and ex vivo, and to explore the role that microvasculature changes play in the initiation and progression of multiple organ injuries in DJES.
Section snippets
Animal handling and ethics statement
Male Sprague–Dawley (SD) rats (280 ± 20 g) and male Kunming mice (20 ± 2 g) were provided by the Laboratory Animal Center of the Second Military Medical University, Shanghai. All were procured from the animal care facility at the university where they were housed in cages with 12/12 h light/dark cycle at 22 ± 2 °C and given standard diets plus water ad libitum. The investigation was carried out in conformity with the requirements of the Ethics Committee of the Second Military Medical University
Microvasculature changes induced by TE in vivo
Synchrotron radiation X-ray angiography showed that the microvasculature of whole-body mouse from the control group had a normal morphology. As shown in Fig. 1A, the vascular anatomy from the neck to the cavitas pelvis could be clearly observed, especially the main blood vessels in the heart, liver and kidney. In the TE-treated group (Fig. 1C), the large vessels, such as abdominal aorta, common hepatic artery, left renal artery, right renal artery, left common iliac artery, right common iliac
Discussion
In general, there are a variety of toxic components in animal venoms, which may play an important role in subduing prey and defense (White, 2010). Similarly, jellyfish tentacles have specialized cells, called cnidocytes, which contain specialized stinging organelles (nematocysts) and a cocktail of toxins (Burnett, 2001, Cegolon et al., 2013). A contact with the nematocyst-bearing tentacles will cause the simultaneous discharge of thousands of venom-filled nematocysts into the skin of the
Conclusions
In summary, using a third-generation synchrotron radiation facility, we confirmed that TE could induce significant microvasculature alterations and hemorrhagic effects in DJES models in vivo and ex vivo. The methods we employed here will probably facilitate further studies on developing effective intervention strategies against DJES.
Acknowledgments
This research was funded by the Scientific Research Starting Foundation for Young Teachers in the Second Military Medical University (2012QN05), the National Natural Science Foundation of China (81370833) and the National High Technology Research and Development Program of China (863 Program) (2013AA092904). The authors thank Pro. Huixin Hong from the Fisheries College of Jimei University for his careful identification of the jellyfish species and Mr. Fang Wei from the College of International
References (35)
- et al.
Automated tracing and change analysis of angiogenic vasculature from in vivo multiphoton confocal image time series
Microvasc. Res.
(2003) - et al.
Partial purification of box jellyfish (Chironex fleckeri) nematocyst venom isolated at the beachside
Toxicon
(1998) - et al.
High-resolution X-ray computed tomography in geosciences: a review of the current technology and applications
Earth Sci. Rev.
(2013) - et al.
Jellyfish blooms in China: dominant species, causes and consequences
Mar. Pollut. Bull.
(2010) - et al.
Structural considerations of the snake venom metalloproteinases, key members of the M12 reprolysin family of metalloproteinases
Toxicon
(2005) - et al.
Hemorrhage induced by snake venom metalloproteinases: biochemical and biophysical mechanisms involved in microvessel damage
Toxicon
(2005) - et al.
Trophic controls of jellyfish blooms and links with fisheries in the East China Sea
Ecol. Model
(2008) - et al.
In vivo real-time microangiography of the liver in mice using synchrotron radiation
J. Hepatol.
(2004) - et al.
A novel proteinaceous cytotoxin from the northern Scyphozoa Cyanea capillata (L.) with structural homology to cubozoan haemolysins
Toxicon
(2011) - et al.
Scyphozoan jellyfish venom metalloproteinases and their role in the cytotoxicity
Toxicon
(2011)
X-ray microtomography in biology
Micron
Evaluation of rib microstructure in Wistar rats using SR-μCT after radiation therapy simulation for breast cancer
Appl. Radiat. Isot.
A comparison of the toxinological characteristics of two Cassiopea and Aurelia species
Toxicon
Small-animal CT: its difference from, and impact on, clinical CT
Nucl. Instrum. Methods Phys. Res. A
Australian venomous jellyfish, envenomation syndromes, toxins and therapy
Toxicon
Multiple organ dysfunction: a delayed envenomation syndrome caused by tentacle extract from the jellyfish Cyanea capillata
Toxicon
Comparison of haemolytic activity of tentacle-only extract from jellyfish Cyanea capillata in diluted whole blood and erythrocyte suspension: diluted whole blood is a valid test system for haemolysis study
Exp. Toxicol. Pathol.
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