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Differential myotoxic and cytotoxic activities of pre-synaptic neurotoxins from Papuan taipan (Oxyuranus scutellatus) and Irian Jayan death adder (Acanthophis rugosus) venoms.
Basic Clin Pharmacol Toxicol. 2013 May; 112(5):325-34.BC

Abstract

Pre-synaptic PLA(2) neurotoxins are important components of many Australasian elapid snake venoms. These toxins disrupt neurotransmitter release. Taipoxin, a pre-synaptic neurotoxin isolated from the venom of the coastal taipan (Oxyuranus scutellatus), causes necrosis and muscle degeneration. The present study examined the myotoxic and cytotoxic activities of venoms from the Papuan taipan (O. scutellatus) and Irian Jayan death adder (Acanthophis rugosus), and also tested their pre-synaptic neurotoxins: cannitoxin and P-EPTX-Ar1a. Based on size-exclusion chromatography analysis, cannitoxin represents 16% of O. scutellatus venom, while P-EPTX-Ar1a represents 6% of A. rugosus venom. In the chick biventer cervicis nerve-muscle preparation, A. rugosus venom displayed significantly higher myotoxic activity than O. scutellatus venom as indicated by inhibition of direct twitches, and an increase in baseline tension. Both cannitoxin and P-EPTX-Ar1a displayed marked myotoxic activity. A. rugosus venom (50-300 μg/ml) produced concentration-dependent inhibition of cell proliferation in a rat skeletal muscle cell line (L6), while 300 μg/ml of O. scutellatus venom was required to inhibit cell proliferation, following 24-hr incubation. P-EPTX-Ar1a had greater cytotoxicity than cannitoxin, inhibiting cell proliferation after 24-hr incubation in L6 cells. Lactate dehydrogenase levels were increased after 1-hr incubation with A. rugosus venom (100-250 μg/ml), O. scutellatus venom (200-250 μg/ml) and P-EPTX-Ar1a (1-2 μM), but not cannitoxin (1-2 μM), suggesting venoms/toxin generated cell necrosis. Thus, A. rugosus and O. scutellatus venoms possess different myotoxic and cytotoxic activities. The proportion of pre-synaptic neurotoxin in the venoms and PLA(2) activity of the whole venoms are unlikely to be responsible for these activities.

Authors+Show Affiliations

Monash Venom Group, Department of Pharmacology, Monash University, Clayton, Vic, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23311944

Citation

Chaisakul, Janeyuth, et al. "Differential Myotoxic and Cytotoxic Activities of Pre-synaptic Neurotoxins From Papuan Taipan (Oxyuranus Scutellatus) and Irian Jayan Death Adder (Acanthophis Rugosus) Venoms." Basic & Clinical Pharmacology & Toxicology, vol. 112, no. 5, 2013, pp. 325-34.
Chaisakul J, Parkington HC, Isbister GK, et al. Differential myotoxic and cytotoxic activities of pre-synaptic neurotoxins from Papuan taipan (Oxyuranus scutellatus) and Irian Jayan death adder (Acanthophis rugosus) venoms. Basic Clin Pharmacol Toxicol. 2013;112(5):325-34.
Chaisakul, J., Parkington, H. C., Isbister, G. K., Konstantakopoulos, N., & Hodgson, W. C. (2013). Differential myotoxic and cytotoxic activities of pre-synaptic neurotoxins from Papuan taipan (Oxyuranus scutellatus) and Irian Jayan death adder (Acanthophis rugosus) venoms. Basic & Clinical Pharmacology & Toxicology, 112(5), 325-34. https://doi.org/10.1111/bcpt.12048
Chaisakul J, et al. Differential Myotoxic and Cytotoxic Activities of Pre-synaptic Neurotoxins From Papuan Taipan (Oxyuranus Scutellatus) and Irian Jayan Death Adder (Acanthophis Rugosus) Venoms. Basic Clin Pharmacol Toxicol. 2013;112(5):325-34. PubMed PMID: 23311944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential myotoxic and cytotoxic activities of pre-synaptic neurotoxins from Papuan taipan (Oxyuranus scutellatus) and Irian Jayan death adder (Acanthophis rugosus) venoms. AU - Chaisakul,Janeyuth, AU - Parkington,Helena C, AU - Isbister,Geoffrey K, AU - Konstantakopoulos,Nicki, AU - Hodgson,Wayne C, Y1 - 2013/02/23/ PY - 2012/10/16/received PY - 2012/12/23/accepted PY - 2013/1/15/entrez PY - 2013/1/15/pubmed PY - 2013/10/25/medline SP - 325 EP - 34 JF - Basic & clinical pharmacology & toxicology JO - Basic Clin. Pharmacol. Toxicol. VL - 112 IS - 5 N2 - Pre-synaptic PLA(2) neurotoxins are important components of many Australasian elapid snake venoms. These toxins disrupt neurotransmitter release. Taipoxin, a pre-synaptic neurotoxin isolated from the venom of the coastal taipan (Oxyuranus scutellatus), causes necrosis and muscle degeneration. The present study examined the myotoxic and cytotoxic activities of venoms from the Papuan taipan (O. scutellatus) and Irian Jayan death adder (Acanthophis rugosus), and also tested their pre-synaptic neurotoxins: cannitoxin and P-EPTX-Ar1a. Based on size-exclusion chromatography analysis, cannitoxin represents 16% of O. scutellatus venom, while P-EPTX-Ar1a represents 6% of A. rugosus venom. In the chick biventer cervicis nerve-muscle preparation, A. rugosus venom displayed significantly higher myotoxic activity than O. scutellatus venom as indicated by inhibition of direct twitches, and an increase in baseline tension. Both cannitoxin and P-EPTX-Ar1a displayed marked myotoxic activity. A. rugosus venom (50-300 μg/ml) produced concentration-dependent inhibition of cell proliferation in a rat skeletal muscle cell line (L6), while 300 μg/ml of O. scutellatus venom was required to inhibit cell proliferation, following 24-hr incubation. P-EPTX-Ar1a had greater cytotoxicity than cannitoxin, inhibiting cell proliferation after 24-hr incubation in L6 cells. Lactate dehydrogenase levels were increased after 1-hr incubation with A. rugosus venom (100-250 μg/ml), O. scutellatus venom (200-250 μg/ml) and P-EPTX-Ar1a (1-2 μM), but not cannitoxin (1-2 μM), suggesting venoms/toxin generated cell necrosis. Thus, A. rugosus and O. scutellatus venoms possess different myotoxic and cytotoxic activities. The proportion of pre-synaptic neurotoxin in the venoms and PLA(2) activity of the whole venoms are unlikely to be responsible for these activities. SN - 1742-7843 UR - https://www.unboundmedicine.com/medline/citation/23311944/Differential_myotoxic_and_cytotoxic_activities_of_pre_synaptic_neurotoxins_from_Papuan_taipan__Oxyuranus_scutellatus__and_Irian_Jayan_death_adder__Acanthophis_rugosus__venoms_ L2 - https://doi.org/10.1111/bcpt.12048 DB - PRIME DP - Unbound Medicine ER -