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Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell’s Viper (Daboia russelii) Envenoming
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نویسنده
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silva a. ,johnston c. ,kuruppu s. ,kneisz d. ,maduwage k. ,kleifeld o. ,smith a.i. ,siribaddana s. ,buckley n.a. ,hodgson w.c. ,isbister g.k.
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منبع
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plos neglected tropical diseases - 2016 - دوره : 10 - شماره : 12
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چکیده
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Background: 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. methodology and findings: 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 a2toxins 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. conclusion: the study shows that myotoxicity in sri lankan russell’s viper envenoming is mild and non-life threatening,and due to two pla2toxins with weak myotoxic properties. © 2016 silva et al.
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آدرس
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monash venom group,department of pharmacology,biomedicine discovery institute,monash university,melbourne,vic,australia,faculty of medicine and allied sciences,rajarata university of sri lanka,saliyapura,sri lanka,south asian clinical toxicology research collaboration,university of peradeniya,peradeniya, Sri Lanka, clinical toxicology research group,university of newcastle,newcastle,nsw, Australia, monash venom group,department of pharmacology,biomedicine discovery institute,monash university,melbourne,vic,australia,department of biochemistry and molecular biology,biomedicine discovery institute,monash university,melbourne,vic, Australia, monash venom group,department of pharmacology,biomedicine discovery institute,monash university,melbourne,vic, Australia, south asian clinical toxicology research collaboration,university of peradeniya,peradeniya,sri lanka,clinical toxicology research group,university of newcastle,newcastle,nsw,australia,department of biochemistry,faculty of medicine,university of peradeniya,peradeniya, Sri Lanka, department of biochemistry and molecular biology,biomedicine discovery institute,monash university,melbourne,vic, Australia, department of biochemistry and molecular biology,biomedicine discovery institute,monash university,melbourne,vic, Australia, faculty of medicine and allied sciences,rajarata university of sri lanka,saliyapura, Sri Lanka, south asian clinical toxicology research collaboration,university of peradeniya,peradeniya,sri lanka,clinical pharmacology,university of sydney,sydney, Australia, monash venom group,department of pharmacology,biomedicine discovery institute,monash university,melbourne,vic, Australia, monash venom group,department of pharmacology,biomedicine discovery institute,monash university,melbourne,vic,australia,south asian clinical toxicology research collaboration,university of peradeniya,peradeniya,sri lanka,clinical toxicology research group,university of newcastle,newcastle,nsw, Australia
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Authors
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