Karabuva Svjetlana, Lukšić Boris, Brizić Ivica, Latinović Zorica, Leonardi Adrijana, Križaj Igor
Clinical Department of Infectious Diseases, University Hospital of Split, Šoltanska 1, Split, Croatia.
Clinical Department of Infectious Diseases, University Hospital of Split, Šoltanska 1, Split, Croatia; University of Split School of Medicine, Šoltanska 2, Split, Croatia.
Toxicon. 2017 Dec 1;139:94-100. doi: 10.1016/j.toxicon.2017.10.003. Epub 2017 Oct 10.
Venom of the nose-horned viper (V. a. ammodytes) as also venoms of some related European viperids can induce also cardiotoxic effects in mammals. In this work we demonstrated that the protein in the V. a. ammodytes venom acting on heart is a myotoxic secreted phospholipase A analogue ammodytin L (AtnL). In the isolated perfused rat heart AtnL induced significant and irreversible cardiotoxicity characterized by atrioventricular (AV) blockade. This venom protein induced appearance of high levels of creatine kinase, lactate dehydrogenase, aspartate aminotransferase and troponin I in the sinus effluent of the isolated heart, indicative for myocardial damage, which is obviously the primary cause of its cardiotoxic action. Gel filtration chromatography subfractions C1 and C2 of the V. a. ammodytes venom harboured most of the venom cardiotoxicity. As we showed, just these two subfractions contained also AtnL. Subfraction C1 in the final CF concentration 11.3 μg/mL (containing 3.1 μg/mL AtnL) induced a complete cardiac arrest while subfraction C2 in the final CF concentration 6.0 μg/mL (containing 0.8 μg/mL AtnL) and the pure AtnL (1.0 μg/mL) did not. Contrary to AtnL, subfraction C1 at 11.3 μg/mL was not able to induce the AV blockade. This exposed the only other cardiotoxic subfractions-specific venom protein, a cysteine-rich secretory protein (CRISP), as an additional venom component potentially involved in modulation of the heart activity. Cardiotoxicity reported in some cases of the adder (V. berus) venom and the asp viper (V. aspis) venom poisonings may be assigned to AtnL in these venoms.
角蝰（极北蝰指名亚种）的毒液以及一些相关欧洲蝰蛇科蛇类的毒液，在哺乳动物体内也会引发心脏毒性效应。在本研究中，我们证实了极北蝰指名亚种毒液中作用于心脏的蛋白质是一种具有肌毒性的分泌型磷脂酶A类似物——角蝰毒素L（AtnL）。在离体灌注大鼠心脏实验中，AtnL引发了显著且不可逆的心脏毒性，其特征为房室传导阻滞。这种毒液蛋白使离体心脏窦房流出液中肌酸激酶、乳酸脱氢酶、天冬氨酸转氨酶和肌钙蛋白I的水平升高，这表明心肌受到了损伤，显然这是其心脏毒性作用的主要原因。角蝰指名亚种毒液的凝胶过滤层析亚组分C1和C2具有大部分的毒液心脏毒性。正如我们所展示的，恰恰这两个亚组分也含有AtnL。最终CF浓度为11.3 μg/mL的亚组分C1（含有3.1 μg/mL AtnL）可导致完全性心脏骤停，而最终CF浓度为6.0 μg/mL的亚组分C2（含有0.8 μg/mL AtnL）和纯AtnL（1.0 μg/mL）则不会。与AtnL相反，11.3 μg/mL的亚组分C1无法诱导房室传导阻滞。这揭示了另一种仅存在于具有心脏毒性的亚组分中的毒液蛋白——富含半胱氨酸的分泌蛋白（CRISP），它可能是另一种参与调节心脏活动的毒液成分。在某些蝮蛇（极北蝰）毒液和角蝰毒液中毒病例中报告的心脏毒性，可能归因于这些毒液中的AtnL。
