MYOTOXIC ACTIVITY OF THE CRUDE VENOM AND THE PRINCIPAL NEUROTOXIN, TAIPOXIN, OF THE AUSTRALIAN TAIPAN, Oxyuranus scutellatus

Abstract

The crude venom of the Australian taipan, Oxyuranus scutellatus and its principal neurotoxin, taipoxin, were injected into the anterolateral aspect of one hind limb of the rat. The effects of the venom and toxin on the morphology and physiology on the underlying soleus muscles were examined. Both the crude venom and the toxin caused necrosis and degeneration of the muscle. Damage to the peripheral muscle fibres could be seen at the light microscopic level as early as 3 h after injection of the toxic compounds. The necrotic response was accompanied by an infiltration of phagocytic cells and an extensive oedema. The wet weight of the damaged muscles was almost doubled by 6 h. In individual muscle fibres, necrosis was associated with the disruption of the plasma membrane and the disorganization of the myofibrils. The basal lamina of the muscle fibres was left intact. Denervated mammalian muscles and innervated avian muscles were also destroyed by taipoxin, but immature avian muscle growing in tissue culture was resistant. Of the 3 subunits of taipoxin, only the basic α‐taipoxin was itself myotoxic. However, its potency was enhanced by the presence of the acid γ‐subunit. The role of the neutral β‐subunit is unclear. The period of necrosis and degeneration lasted for approximately 48 h, after which the muscle fibres began to regenerate. Regeneration took place within the surviving basal lamina, with the formation of myotubes by three days, and small, immature muscle fibres by five days. Regeneration was virtually complete by 21 days.

Modulation of Muscle Regeneration, Myogenesis, and Adipogenesis by the Rho Family Guanine Nucleotide Exchange Factor GEFT

“…Day-to-day wear and tear of adult skeletal muscle accounts for approximately 1 to 2% replacement of muscle fibers per week (75); however, mammalian skeletal muscle has the ability to induce an extensive regeneration in response to severe damage. The use of myotoxins such as bupivacaine, cardiotoxin, and notexin is perhaps the easiest and most reproducible way to induce muscle regeneration in animal models (23,(36)(37)(38)(39). Muscle regeneration, both physically and chemically induced, is characterized by two phases: a degenerative phase and a regenerative phase.…”

“…The process of muscle regeneration, whether induced by everyday or debilitating disease-induced damage, remains an active process for long periods of time after the initial muscle injury. The capacity of tissue for repair occurs via satellite stem cells located between the basal lamina and the sarcolemma in mature skeletal myofibers (39). Upon muscle injury, satellite cells exit G 0 and enter the cell cycle to proliferate.…”

Purification and characterization of a glycoprotein inhibitor of toxic phospholipase from Withania somnifera

“…Generally, elapid venoms exhibit the second type of myonecrosis due to the presence of either myotoxic phospholipases or cardiotoxins in the venoms. Ownby and Colberg [56] noted that the N. naja venom-induced myonecrosis observed was similar to that induced by the phospholipase myotoxins such as notexin, taipoxin, crotoxin, and Bothrops species myotoxins [57][58][59][60][61]. Numerous specific toxic phopholipase A 2 Õs have been isolated from elapid venoms like Pseudechis australis venom.…”

Histopathological analysis and in situ localisation of Australian tiger snake venom in two clinically envenomed domestic animals

“…Harris et al (Harris et al 1975(Harris et al , 2003Harris and MacDonell 1981;White 1987) showed that the purified notexin caused destruction of the myofibres in a mosaic pattern and Preston et al, (1990) (Preston et al 1990 found a dose-dependent relationship between the extent of muscle loss and the amount of venom injected in experimental animals. The feline muscle tissue in this study also clearly showed myotoxicity with an inflammatory response as defined by Mebs and Ownby, (1990) (Mebs and Ownby 1990) and Harris and Maltin (Harris and Maltin 1982), respectively.…”