title: Phospholipase A2-dependent effects of the venom from the New Guinean small-eyed snake Micropechis ikaheka.
abstract: The New Guinean small-eyed snake (Micropechis ikaheka) is a cause of life-threatening envenoming. Previous studies on M. ikaheka venom have indicated the presence of neurotoxins as well as myotoxins. This study examined the in vitro myotoxic effects of M. ikaheka venom and the efficacy of a polyvalent antivenom in neutralizing these effects. Venom (50 microg/ml) produced a slowly developing contracture and inhibition of direct twitches of the chick biventer cervicis nerve-muscle preparation in the presence of tubocurarine (10 microM). Myotoxicity was confirmed by subsequent histological examination of tissues. This myotoxicity was prevented by the prior addition of polyvalent snake antivenom (30 U/ml). However, the addition of antivenom (30 U/ml) 1 h after venom administration failed to reverse or prevent the further inhibition of direct twitches. In addition, venom (1-10 microg/ml) produced concentration-dependent contractions of the guinea-pig isolated ileum. These effects were dependent on phospholipase A2 (PLA2) activity of the venom as evidenced by the ability of the PLA2 inhibitor 4-bromophenacyl bromide (4-BPB; 1.8 mM) to prevent this activity. This study indicates that M. ikaheka venom causes significant myotoxicity and that polyvalent snake antivenom may be a potential treatment for the myotoxic effects in patients envenomed by this species.
authors.affiliation: Monash Venom Group, Department of Pharmacology, Building 13E, Monash University, Victoria 3800, Australia.
authors.forename: Sanjaya
authors.initials: S
authors.lastname: Kuruppu
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Hodgson
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000997:Antivenins / Q000494:pharmacology; D002645:Chickens; D004546:Elapid Venoms / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2
chemical_list: D000098:Acetophenones; D000997:Antivenins; D004546:Elapid Venoms; D004791:Enzyme Inhibitors; D009498:Neurotoxins; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide