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Differential Myotoxic and Cytotoxic Activities of Pre‐synaptic Neurotoxins from Papuan Taipan ( O xyuranus scutellatus ) and Irian Jayan Death Adder ( A canthophis rugosus ) Venoms
Author(s) -
Chaisakul Janeyuth,
Parkington Helena C.,
Isbister Geoffrey K.,
Konstantakopoulos Nicki,
Hodgson Wayne C.
Publication year - 2013
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12048
Subject(s) - venom , neurotoxin , biology , naja , pharmacology , biochemistry
Pre‐synaptic PLA 2 neurotoxins are important components of many A ustralasian elapid snake venoms. These toxins disrupt neurotransmitter release. Taipoxin, a pre‐synaptic neurotoxin isolated from the venom of the coastal taipan ( O xyuranus scutellatus ), causes necrosis and muscle degeneration. The present study examined the myotoxic and cytotoxic activities of venoms from the P apuan taipan ( O . scutellatus ) and I rian J ayan death adder ( A canthophis rugosus ), and also tested their pre‐synaptic neurotoxins: cannitoxin and P ‐ EPTX ‐ A r1a. Based on size‐exclusion chromatography analysis, cannitoxin represents 16% of O . scutellatus venom, while P ‐ EPTX ‐ A r1a 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 ‐ A r1a 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 ‐ A r1a (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.