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.