Silva Anjana, Johnston Christopher, Kuruppu Sanjaya, Kneisz Daniela, Maduwage Kalana, Kleifeld Oded, Smith A Ian, Siribaddana Sisira, Buckley Nicholas A, Hodgson Wayne C, Isbister Geoffrey K
Monash Venom Group, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia.
Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka.
PLoS Negl Trop Dis. 2016 Dec 2;10(12):e0005172. doi: 10.1371/journal.pntd.0005172. eCollection 2016 Dec.
Sri Lankan Russell's viper (Daboia russelii) envenoming is reported to cause myotoxicity and neurotoxicity, which are different to the effects of envenoming by most other populations of Russell's vipers. This study aimed to investigate evidence of myotoxicity in Russell's viper envenoming, response to antivenom and the toxins responsible for myotoxicity.
Clinical features of myotoxicity were assessed in authenticated Russell's viper bite patients admitted to a Sri Lankan teaching hospital. Toxins were isolated using high-performance liquid chromatography. In-vitro myotoxicity of the venom and toxins was investigated in chick biventer nerve-muscle preparations. Of 245 enrolled patients, 177 (72.2%) had local myalgia and 173 (70.6%) had local muscle tenderness. Generalized myalgia and muscle tenderness were present in 35 (14.2%) and 29 (11.8%) patients, respectively. Thirty-seven patients had high (>300 U/l) serum creatine kinase (CK) concentrations in samples 24h post-bite (median: 666 U/l; maximum: 1066 U/l). Peak venom and 24h CK concentrations were not associated (Spearman's correlation; p = 0.48). The 24h CK concentrations differed in patients without myotoxicity (median 58 U/l), compared to those with local (137 U/l) and generalised signs/symptoms of myotoxicity (107 U/l; p = 0.049). Venom caused concentration-dependent inhibition of direct twitches in the chick biventer cervicis nerve-muscle preparation, without completely abolishing direct twitches after 3 h even at 80 μg/ml. Indian polyvalent antivenom did not prevent in-vitro myotoxicity at recommended concentrations. Two phospholipase A2 toxins with molecular weights of 13kDa, U1-viperitoxin-Dr1a (19.2% of venom) and U1-viperitoxin-Dr1b (22.7% of venom), concentration dependently inhibited direct twitches in the chick biventer cervicis nerve-muscle preparation. At 3 μM, U1-viperitoxin-Dr1a abolished twitches, while U1-viperitoxin-Dr1b caused 70% inhibition of twitch force after 3h. Removal of both toxins from whole venom resulted in no in-vitro myotoxicity.
The study shows that myotoxicity in Sri Lankan Russell's viper envenoming is mild and non-life threatening, and due to two PLA2 toxins with weak myotoxic properties.
据报道，斯里兰卡锯鳞蝰（Daboia russelii）咬伤会导致肌毒性和神经毒性，这与大多数其他锯鳞蝰种群咬伤的影响不同。本研究旨在调查锯鳞蝰咬伤中肌毒性的证据、抗蛇毒血清的反应以及导致肌毒性的毒素。
对入住斯里兰卡一家教学医院的经证实的锯鳞蝰咬伤患者的肌毒性临床特征进行了评估。使用高效液相色谱法分离毒素。在鸡双腹肌神经 - 肌肉标本中研究了毒液和毒素的体外肌毒性。在245名登记患者中，177名（72.2%）有局部肌痛，173名（70.6%）有局部肌肉压痛。分别有35名（14.2%）和29名（11.8%）患者出现全身肌痛和肌肉压痛。37名患者在咬伤后24小时的样本中血清肌酸激酶（CK）浓度高（>300 U/l）（中位数：666 U/l；最大值：1066 U/l）。毒液峰值与24小时CK浓度无关（斯皮尔曼相关性；p = 0.48）。与无肌毒性的患者（中位数58 U/l）相比，有局部（137 U/l）和全身肌毒性体征/症状的患者（107 U/l）的24小时CK浓度有所不同（p = 0.049）。毒液在鸡双腹肌神经 - 肌肉标本中引起浓度依赖性的直接抽搐抑制，即使在80μg/ml时3小时后也未完全消除直接抽搐。印度多价抗蛇毒血清在推荐浓度下不能预防体外肌毒性。两种分子量为13kDa的磷脂酶A2毒素，U1 - 蝰蛇毒素 - Dr1a（占毒液的19.2%）和U1 - 蝰蛇毒素 - Dr1b（占毒液的22.7%），在鸡双腹肌神经 - 肌肉标本中浓度依赖性地抑制直接抽搐。在3μM时，U1 - 蝰蛇毒素 - Dr1a消除了抽搐，而U1 - 蝰蛇毒素 - Dr1b在3小时后导致抽搐力抑制70%。从全毒液中去除这两种毒素后，体外无肌毒性。
该研究表明，斯里兰卡锯鳞蝰咬伤中的肌毒性较轻，无生命危险，是由两种肌毒性较弱的磷脂酶A2毒素引起的。
