Differential Myotoxic and Cytotoxic Activities of Pre‐synaptic Neurotoxins from Papuan Taipan (Oxyuranus scutellatus) and Irian Jayan Death Adder (Acanthophis rugosus) Venoms

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 lg/ml) produced concentration-dependent inhibition of cell proliferation in a rat skeletal muscle cell line (L6), while 300 lg/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 lg/ml), O. scutellatus venom (200-250 lg/ml) and P-EPTX-Ar1a (1-2 lM), but not cannitoxin (1-2 lM), 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.While snake envenoming is an infrequent occurrence in Australia, it remains an important cause of morbidity and mortality in Papua New Guinea and Irian Jaya [1,2]. Myotoxicity is a critical outcome of systemic toxicity produced by many Australasian elapids, including rarely with death adders (genus Acanthophis) and taipans (genus Oxyuranus). It has been suggested that phospholipase A 2 (PLA 2 ) is the major venom component responsible for myotoxicity [3][4][5]. Indeed, many snake venoms and isolated PLA 2 toxins display myotoxicity and cytotoxicity (e.g. Lys-49 phospholipase A 2 of Bothrops asper snake venom) [6-10] which induce membrane disruption and Ca 2+ influx.Although the Papuan taipan has been regarded as a separate subspecies to the Australian populations, recent taxonomic studies have indicated no significant differentiation between the two populations [11,12]. The clinical features of systemic taipan envenoming include venom-induced consumption coagulopathy, renal toxicity, cardiac disturbances and a descending neuromuscular paralysis [13][14][15]. The venom of the Australian coastal taipan has myotoxic activity causing necrosis and degeneration of mammalian muscle [16]. In contr...

Venom Down Under: Dynamic Evolution of Australian Elapid Snake Toxins

“…Such complexes have recently been reported to be present in the venoms of Acanthophis sp . [60,61,62,63]. …”

Snake Venom Cytotoxins, Phospholipase A2s, and Zn2+-dependent Metalloproteinases: Mechanisms of Action and Pharmacological Relevance

“…The major types of biomolecules found in snake venom are proteins, some of which are enzymes whereas other proteins lack catalytic activity. The most potent toxins of snake venom, which are responsible for causing severe pathophysiological effects after envenomation, are α-neurotoxins – non-enzymatic nAChRs binding proteins [5,6], β-neurotoxins – pre-synaptic phospholipase A2 (PLA2) [7–9] and pre-synaptic phospholipase A 2 (PLA 2 ), β-neurotoxins [7–9], cytotoxins [10–16] non-neurotoxic PLA 2 s [17–20], and Zn 2+ -dependent metalloproteinases [21]. All of these toxins will be briefly reviewed in this section and more extensively in the ensuing sections of this review.…”

Gross and Histopathological Dermal Changes at Sites of Snakebite – Report from Autopsy Series

“…World Health Organization aims to eradicate bite injury due to snake which is a public health problem in tropical areas of the world. Agriculture is the mainstream of employment which accounts for 8,660 mortalities in a year 13 . Histopathological results can be helpful in establishing the cause of death in those snake bite cases where other circumstantial shreds of evidence are lacking 13,14 .…”