The effects of antivenom on the in vitro neurotoxicity of venoms from the taipans Oxyuranus scutellatus, Oxyuranus microlepidotus and Oxyuranus scutellatus canni

被引:33
作者
Crachi, MT [1 ]
Hammer, LW [1 ]
Hodgson, WC [1 ]
机构
[1] Monash Univ, Dept Pharmacol, Monash Venom Grp, Clayton, Vic 3168, Australia
基金
澳大利亚研究理事会;
关键词
D O I
10.1016/S0041-0101(99)00118-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The venoms of the inland (Oxyuranus microlepidotus), coastal (O. scutellatus) and Paguan (O. s. canni) taipans are among the most potent in the world. The present study compared the in vitro neurotoxic effects of these venoms and the protective effects of taipan antivenom. Venom (10 mu g/ml) from all three snakes abolished nerve-mediated twitches of the chick biventer cervicis muscle preparation with the following rank order of potency (based on the time taken to inhibit 90% of the twitch response; t(90)): O. microlepidotus (27 +/- 3 min) > O. scutellatus (42 +/- 3 min) = O. S. canni (48 +/- 5 min). This inhibitory effect of all three venoms was primarily postsynaptic in origin as evidenced by the inhibition of responses to exogenous acetylcholine (ACh; 1 mM) and carbachol (CCh; 20 mu M); but not potassium chloride (40 mM). In contrast, the presynaptic neurotoxins taipoxin (3 mu g/ml) and paradoxin (3 mu g/ml) abolished nerve-mediated twitches without producing a significant effect on contractile responses to exogenous agonists. Prior incubation of the tissue with taipan antivenom (1 unit/ml for 10 min) markedly attenuated the inhibitory effects of taipoxin (3 mu g/ml) and paradoxin (3 mu g/ml), as well as O. scutellatus (10 mu g/ml) and O. s. canni (10 mu g/ml) venom. However, in the presence of antivenom, O. microlepidotus venom (10 mu g/ml) still abolished nerve-mediated twitches and responses to ACh and CCh. The results of the current study indicate that taipan antivenom, raised against O. scutellatus venom, is effective, in vitro, against the neurotoxic effects of venom from the Papuan and coastal taipans, as well as the presynaptic effects of venom from the inland taipan. However, the antivenom appears less effective against the postsynaptic effects of the latter. It is possible that inland taipan venom contains a component not neutralised by the antivenom which may contribute to the extreme potency of this venom. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1771 / 1778
页数:8
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