A comparative study on the equine and camelid antivenoms upon cardiovascular changes induced with Hemiscorpius lepturus venom in rats

Document Type: Original Article

Authors

1 Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Aquatic Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

3 The Persian Gulf Tropical Research Center, Biochemistry Group, Bushehr University of Medical Sciences, Bushehr, Iran

4 Department of Physiology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran

5 College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea

6 Biotechnology Research Center, Venom and Biotherapeutics Molecules Laboratory, Pasteur Institute of Iran, Tehran, Iran

7 Department of Human Vaccine and Serum, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj, Iran

8 School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran

9 Department of Pharmacology, Bushehr University of Medical Sciences, Bushehr, Iran

10.22038/ijbms.2019.14052

Abstract

Objective(s): In this study, the neutralizing abilities of the equine and the recently introduced camelid antivenoms on the hemodynamic parameters (inotropism, chronotropism, and arrhythmogenicity) were assessed following envenomation by Hemiscorpius lepturus venom in rats.
Materials and Methods: At first, the electrophoretic profiles of both products were obtained by using the SDS-PAGE method (12.5%) and stained with Coomassie blue and silver nitrate. Secondly, different doses of the camelid antivenom (10, 50, and 100 µl) were given intravenously in 10 min before venom injection (400 µg/rat). The neutralizing potencies of camelid and equine antivenoms were measured by preincubation (100 µl) with H. lepturus venom for 30 min at room temperature. Finally, equal amounts of the antivenoms were injected intravenously to observe the hemodynamic changes.
Results: Based on the electrophoretic profile, it was evident that undesired proteins significantly decreased in equine antivenom, owing to impurities. Pretreatment with the camelid antivenom (100 µl), neutralized the elevation of the mean arterial pressure evoked with scorpion venom injection (88.15±4.56 versus 10.2±1.23 percent at the 8th min). The Incubation of the venom and the camelid antivenom counteracted the hemodynamic changes, but the equine product had no effect. The intravascular injection of the equine antivenom transiently increased the mean arterial pressure as compared to the control (108.67±8.63 mmHg versus 52.67±1.93 mmHg at the 10th min).
Conclusion: The most obvious finding emerging from this study was that the camelid antivenom neutralized the hemodynamic changes in rats significantly, but in comparison, the equine antivenom had just a minor ability.

Keywords


1. Dunlop JA, Selden PA. Scorpion fragments from the Silurian of Powys, Wales. J Arachnol 2013;16:27-32.
2. Shahbazzadeh D, Amirkhani A, Djadid ND, Bigdeli S, Akbari A, Ahari H, et al. Epidemiological and clinical survey of scorpionism in Khuzestan province, Iran (2003). Toxicon 2009;53:454-459.
3. Gueron M, Ilia R, Sofer S. The cardiovascular system after scorpion envenomation. A review. J Toxicol Clin Toxico 1992;30:245-258.
4. Gueron M, Yaron R. Cardiovascular manifestations of severe scorpion sting: clinicopathologic correlations. Chest 1970;57:156-162.
5. Jalali A, Rahim F. Epidemiological review of scorpion envenomation in Iran. Iran J Pharmaceu Res 2014;13:743-756
6. Valavi E, Ansari MA. Hemolytic uremic syndrome following Hemiscorpius lepturus (scorpion) sting. Indian J Nephrol 2008;18:166-168.
7. Alirahimi E, Kazemi-Lomedasht F, Shahbazzadeh D, Habibi-Anbouhi M, Hosseininejad-Chafi M, Sotoudeh N, et al. Nanobodies as novel therapeutic agents in envenomation. BBA-General Subjects 2018;2955-2965.
8. Ismail M, Abd-Elsalam M. Pharmacokinetics of 125I-labelled IgG, F (ab′) 2 and Fab fractions of scorpion and snake antivenins: merits and potential for therapeutic use. Toxicon 1998;36:1523-1528.
9. Freire-Maia L, Campos J, Amaral C. Approaches to the treatment of scorpion envenoming. Toxicon 1994;32:1009-1014.
10. Cook DA, Samarasekara CL, Wagstaff SC, Kinne J, Wernery U, Harrison RA. Analysis of camelid IgG for antivenom development: Immunoreactivity and preclinical neutralisation of venom-induced pathology by IgG subclasses, and the effect of heat treatment. Toxicon 2010; 56:596-603.
11. Pourkhalili K, Fatemikia H, Kim E, Mashayekhy NR, Dounighi NM, Hajivandi A, et al.  Hemodynamic changes in experimentally envenomed anaesthetized rats by intravenous injection of Hemiscorpius lepturus venom. J Arthropod-Borne Di 2018;12:31-40.
12. Behdani M, Zeinali S, Karimipour M, Shahreza HK, Ghasemi P, Asadzadeh N, et al. Antiserum production in immunized camel by the venom of Hemiscorpius lepturus scorpion: evaluation of neutralizing test in vivo. Tehran Univ Med J 2010;68:268-273.
13. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-254.
14. Chippaux J-P, Goyffon M.Epidemiology of scorpionism: a global appraisal. Acta Trop 2008;107:71-79.
15. Isbister GK, Bawaskar HS. Scorpion envenomation. New England J Med 2014;371:457-463.
16. Dehghani R, Fathi B. Scorpion sting in Iran: a review. Toxicon 2012; 60:919-933.
17. Sofer S, Gueron M Vasodilators and hypertensive encephalopathy following scorpion envenomation in children. Chest 1990; 97:118-120.
18. Cook DA, Owen T, Wagstaff SC, Kinne J, Wernery U, Harrison RA. Analysis of camelid antibodies for antivenom development: Neutralisation of venom-induced pathology. Toxicon 2010;56:373-380.
19. Freire-Maia L, Pinto G, Franco I. Mechanism of the cardiovascular effects produced by purified scorpion toxin in the rat. J Pharmacol Exp Ther 1974;188:207-213
20. Pucca MB, Cerni FA, Junior ELP, Bordon KdCF, Amorim FG, Cordeiro FA, et al. Tityus serrulatus venom–a lethal cocktail. Toxicon 2015;108:272-284.
21. Seyedian R, Pipelzadeh MH, Jalali A, Kim E, Lee H, Kang C, et al. Enzymatic analysis of Hemiscorpius lepturus scorpion venom using zymography and venom-specific antivenin. Toxicon 2010;56:521-525.
22. Lauwereys M, Ghahroudi MA, Desmyter A, Kinne J, Hölzer W, De Genst E, et al. Potent enzyme inhibitors derived from dromedary heavy‐chain antibodies. EMBO J 1998; 17:3512-3520.
23. Lovreček D, Tomić S. A century of antivenom. Collegium Antropol 2011; 35:249-258.
24. Padula AM, Winkel KD. Fatal presumed tiger snake (Notechis scutatus) envenomation in a cat with measurement of venom and antivenom concentration. Toxicon 2016;113:7-10.
25. Padula AM, Winkel KD.Antivenom production in the alpaca (Vicugna pacos): Monovalent and polyvalent antivenom neutralisation of lethal and procoagulant toxins in Australian elapid venoms.Small Rumin Res 2017;149:34-39.
26. Ramasamy S, Isbister GK, Seymour JE, Hodgson WC. The in vivo cardiovascular effects of box jellyfish Chironex fleckeri venom in rats: efficacy of pre-treatment with antivenom, verapamil and magnesium sulphate. Toxicon. 2004;43:685-690.
27. Sofer S, Shahak E, Gueron M. Scorpion envenomation and antivenom therapy. J Pediatr 1994;124:973-978.
28. Abroug F, ElAtrous S, Nouria S, Haguiga H, Touzi N, Bouchoucha S. Serotherapy in scorpion envenomation: a randomised controlled trial. The Lancet 1999;354:906-909
29. Darvish M, Ebrahimi SA, Shahbazzadeh D, Bagheri K-P, Behdani M, Shokrgozar MA Camelid antivenom development and potential in vivo neutralization of Hottentotta saulcyi scorpion venom. Toxicon 2016;113:70-75.