An Examination of the Neutralization of In Vitro Toxicity of Chinese Cobra (<i>Naja atra</i>) Venom by Different Antivenoms
The Chinese Cobra (<i>Naja atra</i>) is an elapid snake of major medical importance in southern China. We describe the in vitro neurotoxic, myotoxic, and cytotoxic effects of <i>N. atra</i> venom, as well as examining the efficacy of three Chinese monovalent antivenoms (<i...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/8/10/377 |
| _version_ | 1797552550770114560 |
|---|---|
| author | Qing Liang Tam Minh Huynh Nicki Konstantakopoulos Geoffrey K. Isbister Wayne C. Hodgson |
| author_facet | Qing Liang Tam Minh Huynh Nicki Konstantakopoulos Geoffrey K. Isbister Wayne C. Hodgson |
| author_sort | Qing Liang |
| collection | DOAJ |
| description | The Chinese Cobra (<i>Naja atra</i>) is an elapid snake of major medical importance in southern China. We describe the in vitro neurotoxic, myotoxic, and cytotoxic effects of <i>N. atra</i> venom, as well as examining the efficacy of three Chinese monovalent antivenoms (<i>N. atra</i> antivenom, <i>Gloydius brevicaudus</i> antivenom and <i>Deinagkistrodon acutus</i> antivenom) and an Australian polyvalent snake antivenom. In the chick biventer cervicis nerve-muscle preparation, <i>N. atra</i> venom (1–10 µg/mL) abolished indirect twitches in a concentration-dependent manner, as well as abolishing contractile responses to exogenous acetylcholine chloride (ACh) and carbamylcholine chloride (CCh), indicative of post-synaptic neurotoxicity. Contractile responses to potassium chloride (KCl) were also significantly inhibited by venom indicating myotoxicity. The prior addition of Chinese <i>N. atra</i> antivenom (0.75 U/mL) or Australian polyvalent snake antivenom (3 U/mL), markedly attenuated the neurotoxic actions of venom (3 µg/mL) and prevented the inhibition of contractile responses to ACh, CCh, and KCl. The addition of Chinese antivenom (0.75 U/mL) or Australian polyvalent antivenom (3 U/mL) at the t<sub>90</sub> time point after the addition of venom (3 µg/mL), partially reversed the inhibition of twitches and significantly reversed the venom-induced inhibition of responses to ACh and CCh, but had no significant effect on the response to KCl. Venom (30 µg/mL) also abolished direct twitches in the chick biventer cervicis nerve-muscle preparation and caused a significant increase in baseline tension, further indicative of myotoxicity. <i>N. atra</i> antivenom (4 U/mL) prevented the myotoxic effects of venom (30 µg/mL). However, <i>G. brevicaudus</i> antivenom (24 U/mL), <i>D. acutus</i> antivenom (8 U/mL) and Australian polyvalent snake antivenom (33 U/mL) were unable to prevent venom (30 µg/mL) induced myotoxicity. In the L6 rat skeletal muscle myoblast cell line, <i>N. atra</i> venom caused concentration-dependent inhibition of cell viability, with a half maximal inhibitory concentration (IC<sub>50</sub>) of 2.8 ± 0.48 μg/mL. <i>N. atra</i> antivenom significantly attenuated the cytotoxic effect of the venom, whereas Australian polyvalent snake antivenom was less effective but still attenuated the cytotoxic effects at lower venom concentrations. Neither <i>G. brevicaudus</i> antivenom or <i>D. acutus</i> antivenom were able to prevent the cytotoxicity. This study indicates that Chinese <i>N. atra</i> monovalent antivenom is efficacious against the neurotoxic, myotoxic and cytotoxic effects of <i>N. atra</i> venom but the clinical effectiveness of the antivenom is likely to be diminished, even if given early after envenoming. The use of Chinese viper antivenoms (i.e., <i>G. brevicaudus</i> and <i>D. acutus</i> antivenoms) in cases of envenoming by the Chinese cobra is not supported by the results of the current study. |
| first_indexed | 2024-03-10T16:02:41Z |
| format | Article |
| id | doaj.art-65eb8269e69042f684ccb261ead44079 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T16:02:41Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-65eb8269e69042f684ccb261ead440792023-11-20T15:07:59ZengMDPI AGBiomedicines2227-90592020-09-0181037710.3390/biomedicines8100377An Examination of the Neutralization of In Vitro Toxicity of Chinese Cobra (<i>Naja atra</i>) Venom by Different AntivenomsQing Liang0Tam Minh Huynh1Nicki Konstantakopoulos2Geoffrey K. Isbister3Wayne C. Hodgson4Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton 3800, AustraliaMonash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton 3800, AustraliaMonash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton 3800, AustraliaMonash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton 3800, AustraliaMonash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton 3800, AustraliaThe Chinese Cobra (<i>Naja atra</i>) is an elapid snake of major medical importance in southern China. We describe the in vitro neurotoxic, myotoxic, and cytotoxic effects of <i>N. atra</i> venom, as well as examining the efficacy of three Chinese monovalent antivenoms (<i>N. atra</i> antivenom, <i>Gloydius brevicaudus</i> antivenom and <i>Deinagkistrodon acutus</i> antivenom) and an Australian polyvalent snake antivenom. In the chick biventer cervicis nerve-muscle preparation, <i>N. atra</i> venom (1–10 µg/mL) abolished indirect twitches in a concentration-dependent manner, as well as abolishing contractile responses to exogenous acetylcholine chloride (ACh) and carbamylcholine chloride (CCh), indicative of post-synaptic neurotoxicity. Contractile responses to potassium chloride (KCl) were also significantly inhibited by venom indicating myotoxicity. The prior addition of Chinese <i>N. atra</i> antivenom (0.75 U/mL) or Australian polyvalent snake antivenom (3 U/mL), markedly attenuated the neurotoxic actions of venom (3 µg/mL) and prevented the inhibition of contractile responses to ACh, CCh, and KCl. The addition of Chinese antivenom (0.75 U/mL) or Australian polyvalent antivenom (3 U/mL) at the t<sub>90</sub> time point after the addition of venom (3 µg/mL), partially reversed the inhibition of twitches and significantly reversed the venom-induced inhibition of responses to ACh and CCh, but had no significant effect on the response to KCl. Venom (30 µg/mL) also abolished direct twitches in the chick biventer cervicis nerve-muscle preparation and caused a significant increase in baseline tension, further indicative of myotoxicity. <i>N. atra</i> antivenom (4 U/mL) prevented the myotoxic effects of venom (30 µg/mL). However, <i>G. brevicaudus</i> antivenom (24 U/mL), <i>D. acutus</i> antivenom (8 U/mL) and Australian polyvalent snake antivenom (33 U/mL) were unable to prevent venom (30 µg/mL) induced myotoxicity. In the L6 rat skeletal muscle myoblast cell line, <i>N. atra</i> venom caused concentration-dependent inhibition of cell viability, with a half maximal inhibitory concentration (IC<sub>50</sub>) of 2.8 ± 0.48 μg/mL. <i>N. atra</i> antivenom significantly attenuated the cytotoxic effect of the venom, whereas Australian polyvalent snake antivenom was less effective but still attenuated the cytotoxic effects at lower venom concentrations. Neither <i>G. brevicaudus</i> antivenom or <i>D. acutus</i> antivenom were able to prevent the cytotoxicity. This study indicates that Chinese <i>N. atra</i> monovalent antivenom is efficacious against the neurotoxic, myotoxic and cytotoxic effects of <i>N. atra</i> venom but the clinical effectiveness of the antivenom is likely to be diminished, even if given early after envenoming. The use of Chinese viper antivenoms (i.e., <i>G. brevicaudus</i> and <i>D. acutus</i> antivenoms) in cases of envenoming by the Chinese cobra is not supported by the results of the current study.https://www.mdpi.com/2227-9059/8/10/377<i>Naja atra</i>neurotoxicitymyotoxicityvenomantivenomsnake |
| spellingShingle | Qing Liang Tam Minh Huynh Nicki Konstantakopoulos Geoffrey K. Isbister Wayne C. Hodgson An Examination of the Neutralization of In Vitro Toxicity of Chinese Cobra (<i>Naja atra</i>) Venom by Different Antivenoms Biomedicines <i>Naja atra</i> neurotoxicity myotoxicity venom antivenom snake |
| title | An Examination of the Neutralization of In Vitro Toxicity of Chinese Cobra (<i>Naja atra</i>) Venom by Different Antivenoms |
| title_full | An Examination of the Neutralization of In Vitro Toxicity of Chinese Cobra (<i>Naja atra</i>) Venom by Different Antivenoms |
| title_fullStr | An Examination of the Neutralization of In Vitro Toxicity of Chinese Cobra (<i>Naja atra</i>) Venom by Different Antivenoms |
| title_full_unstemmed | An Examination of the Neutralization of In Vitro Toxicity of Chinese Cobra (<i>Naja atra</i>) Venom by Different Antivenoms |
| title_short | An Examination of the Neutralization of In Vitro Toxicity of Chinese Cobra (<i>Naja atra</i>) Venom by Different Antivenoms |
| title_sort | examination of the neutralization of in vitro toxicity of chinese cobra i naja atra i venom by different antivenoms |
| topic | <i>Naja atra</i> neurotoxicity myotoxicity venom antivenom snake |
| url | https://www.mdpi.com/2227-9059/8/10/377 |
| work_keys_str_mv | AT qingliang anexaminationoftheneutralizationofinvitrotoxicityofchinesecobrainajaatraivenombydifferentantivenoms AT tamminhhuynh anexaminationoftheneutralizationofinvitrotoxicityofchinesecobrainajaatraivenombydifferentantivenoms AT nickikonstantakopoulos anexaminationoftheneutralizationofinvitrotoxicityofchinesecobrainajaatraivenombydifferentantivenoms AT geoffreykisbister anexaminationoftheneutralizationofinvitrotoxicityofchinesecobrainajaatraivenombydifferentantivenoms AT waynechodgson anexaminationoftheneutralizationofinvitrotoxicityofchinesecobrainajaatraivenombydifferentantivenoms AT qingliang examinationoftheneutralizationofinvitrotoxicityofchinesecobrainajaatraivenombydifferentantivenoms AT tamminhhuynh examinationoftheneutralizationofinvitrotoxicityofchinesecobrainajaatraivenombydifferentantivenoms AT nickikonstantakopoulos examinationoftheneutralizationofinvitrotoxicityofchinesecobrainajaatraivenombydifferentantivenoms AT geoffreykisbister examinationoftheneutralizationofinvitrotoxicityofchinesecobrainajaatraivenombydifferentantivenoms AT waynechodgson examinationoftheneutralizationofinvitrotoxicityofchinesecobrainajaatraivenombydifferentantivenoms |