Inhibition of presynaptic neurotoxins in taipan venom by suramin

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Taipans are amongst the most venomous snakes in the world, and neurotoxicity is a major life-threatening symptom of envenoming by these snakes. Three species of taipans exist, and the venom from each species contains a presynaptic neurotoxin which accounts for much of the neurotoxicity observed following human envenoming. The high cost of antivenom used to treat neurotoxicity has resulted in the need to develop alternative but effective therapies. Therefore, in this study, we examined the ability of the P2Y receptor antagonist suramin to prevent the in vitro neurotoxic effects of the three presynaptic neurotoxins in taipan venoms: taipoxin, paradoxin and cannitoxin. Toxins were purchased from commercial sources or purified in house, using multiple steps of gel filtration chromatography. All three toxins (11 nM) inhibited nerve-mediated twitches in the chick biventer cervicis nerve-muscle preparation within 300 min. The presence of suramin (0.3 mM) completely blocked the taipoxin and cannitoxin-mediated inhibition of nerve-mediated twitches within the course of the experiment (P <0.0001). However, paradoxin induced a 32 decrease in twitch height even in the presence of suramin within 360 min. This was significantly different compared to toxin alone (P <0.0001). We also examined the effect of suramin on the neurotoxic effects of textilotoxin and the products of phospholipase A2 action. Each toxin alone or in the presence of suramin failed to inhibit the responses to exogenous agonists ACh, CCh or KCl. Our results warrant clinical studies aimed determining the efficacy of suramin in preventing the onset of neurotoxicity following taipan envenoming.
Original languageEnglish
Pages (from-to)305 - 310
Number of pages6
JournalNeurotoxicity Research
Volume25
Issue number3
DOIs
Publication statusPublished - 2014

Cite this

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title = "Inhibition of presynaptic neurotoxins in taipan venom by suramin",
abstract = "Taipans are amongst the most venomous snakes in the world, and neurotoxicity is a major life-threatening symptom of envenoming by these snakes. Three species of taipans exist, and the venom from each species contains a presynaptic neurotoxin which accounts for much of the neurotoxicity observed following human envenoming. The high cost of antivenom used to treat neurotoxicity has resulted in the need to develop alternative but effective therapies. Therefore, in this study, we examined the ability of the P2Y receptor antagonist suramin to prevent the in vitro neurotoxic effects of the three presynaptic neurotoxins in taipan venoms: taipoxin, paradoxin and cannitoxin. Toxins were purchased from commercial sources or purified in house, using multiple steps of gel filtration chromatography. All three toxins (11 nM) inhibited nerve-mediated twitches in the chick biventer cervicis nerve-muscle preparation within 300 min. The presence of suramin (0.3 mM) completely blocked the taipoxin and cannitoxin-mediated inhibition of nerve-mediated twitches within the course of the experiment (P <0.0001). However, paradoxin induced a 32 decrease in twitch height even in the presence of suramin within 360 min. This was significantly different compared to toxin alone (P <0.0001). We also examined the effect of suramin on the neurotoxic effects of textilotoxin and the products of phospholipase A2 action. Each toxin alone or in the presence of suramin failed to inhibit the responses to exogenous agonists ACh, CCh or KCl. Our results warrant clinical studies aimed determining the efficacy of suramin in preventing the onset of neurotoxicity following taipan envenoming.",
author = "Kuruppu, {Don Monath Sanjaya} and Janeyuth Chaisakul and Smith, {Alexander Ian} and Hodgson, {Wayne Clarence}",
year = "2014",
doi = "10.1007/s12640-013-9426-z",
language = "English",
volume = "25",
pages = "305 -- 310",
journal = "Neurotoxicity Research",
issn = "1476-3524",
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Inhibition of presynaptic neurotoxins in taipan venom by suramin. / Kuruppu, Don Monath Sanjaya; Chaisakul, Janeyuth; Smith, Alexander Ian; Hodgson, Wayne Clarence.

In: Neurotoxicity Research, Vol. 25, No. 3, 2014, p. 305 - 310.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Inhibition of presynaptic neurotoxins in taipan venom by suramin

AU - Kuruppu, Don Monath Sanjaya

AU - Chaisakul, Janeyuth

AU - Smith, Alexander Ian

AU - Hodgson, Wayne Clarence

PY - 2014

Y1 - 2014

N2 - Taipans are amongst the most venomous snakes in the world, and neurotoxicity is a major life-threatening symptom of envenoming by these snakes. Three species of taipans exist, and the venom from each species contains a presynaptic neurotoxin which accounts for much of the neurotoxicity observed following human envenoming. The high cost of antivenom used to treat neurotoxicity has resulted in the need to develop alternative but effective therapies. Therefore, in this study, we examined the ability of the P2Y receptor antagonist suramin to prevent the in vitro neurotoxic effects of the three presynaptic neurotoxins in taipan venoms: taipoxin, paradoxin and cannitoxin. Toxins were purchased from commercial sources or purified in house, using multiple steps of gel filtration chromatography. All three toxins (11 nM) inhibited nerve-mediated twitches in the chick biventer cervicis nerve-muscle preparation within 300 min. The presence of suramin (0.3 mM) completely blocked the taipoxin and cannitoxin-mediated inhibition of nerve-mediated twitches within the course of the experiment (P <0.0001). However, paradoxin induced a 32 decrease in twitch height even in the presence of suramin within 360 min. This was significantly different compared to toxin alone (P <0.0001). We also examined the effect of suramin on the neurotoxic effects of textilotoxin and the products of phospholipase A2 action. Each toxin alone or in the presence of suramin failed to inhibit the responses to exogenous agonists ACh, CCh or KCl. Our results warrant clinical studies aimed determining the efficacy of suramin in preventing the onset of neurotoxicity following taipan envenoming.

AB - Taipans are amongst the most venomous snakes in the world, and neurotoxicity is a major life-threatening symptom of envenoming by these snakes. Three species of taipans exist, and the venom from each species contains a presynaptic neurotoxin which accounts for much of the neurotoxicity observed following human envenoming. The high cost of antivenom used to treat neurotoxicity has resulted in the need to develop alternative but effective therapies. Therefore, in this study, we examined the ability of the P2Y receptor antagonist suramin to prevent the in vitro neurotoxic effects of the three presynaptic neurotoxins in taipan venoms: taipoxin, paradoxin and cannitoxin. Toxins were purchased from commercial sources or purified in house, using multiple steps of gel filtration chromatography. All three toxins (11 nM) inhibited nerve-mediated twitches in the chick biventer cervicis nerve-muscle preparation within 300 min. The presence of suramin (0.3 mM) completely blocked the taipoxin and cannitoxin-mediated inhibition of nerve-mediated twitches within the course of the experiment (P <0.0001). However, paradoxin induced a 32 decrease in twitch height even in the presence of suramin within 360 min. This was significantly different compared to toxin alone (P <0.0001). We also examined the effect of suramin on the neurotoxic effects of textilotoxin and the products of phospholipase A2 action. Each toxin alone or in the presence of suramin failed to inhibit the responses to exogenous agonists ACh, CCh or KCl. Our results warrant clinical studies aimed determining the efficacy of suramin in preventing the onset of neurotoxicity following taipan envenoming.

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DO - 10.1007/s12640-013-9426-z

M3 - Article

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SP - 305

EP - 310

JO - Neurotoxicity Research

JF - Neurotoxicity Research

SN - 1476-3524

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ER -