BMC Research Notes | |
Comparative in-vivo toxicity of venoms from South Asian hump-nosed pit vipers (Viperidae: Crotalinae: Hypnale) | |
Indika Gawarammana4  Kalana Maduwage1  Danister Weilgama2  Panduka Gunawardena3  Anjana Silva2  | |
[1] School of Medicine and Public Health, University of Newcastle, NSW, Australia;Department of Parasitology, Faculty of Medicine and Allied Sciences Rajarata, University of Sri Lanka, Saliyapura, Sri Lanka;Department of Veterinary Pathobiology, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Peradeniya, Sri Lanka;Department of Medicine, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka | |
关键词: Histopathology; Toxicity; Venom; Zara; Nepa; Hypnale; | |
Others : 1165821 DOI : 10.1186/1756-0500-5-471 |
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received in 2012-06-26, accepted in 2012-08-27, 发布年份 2012 | |
【 摘 要 】
Background
Envenoming by south Asian hump-nosed pit vipers (Genus: Hypnale) is a significant health issue in Sri Lanka and in peninsular India. Bites by these snakes frequently lead to local envenoming, coagulopathy and acute renal failure even resulting in death. Recently the genus was revised and the existence of three species viz H. hypnale, H. nepa and H. zara were recognized. There is, however, a paucity of information on the toxicity of the venoms of these species. Hence, we compared the toxic effects of the three Hypnale venoms using BALB/c mice.
Findings
Intraperitoneal median lethal doses (LD50) for H. hypnale, H. zara and H. nepa venoms were 1.6, 6.0 and 9.5 μg protein/g respectively. Minimum haemorrhagic doses for venoms of H. hypnale, H. zara and H. nepa were 3.4, 11.0 and 16.6 μg protein/mouse respectively. The minimum necrotic doses for the same venoms were 15.0, 55.1 and 68.2 μg protein/mouse respectively. Severe congestion and petecheal haemorrhages were observed in lungs, kidneys, liver and the alimentary tract. Histopathogical examination of kidneys revealed proximal tubular cell injury and acute tubular necrosis with intact basement membrane indicating possible direct nephrotoxicity. Hypnale venoms caused pulmonary oedema, hepatocellular degeneration and necrosis, focal neuronal degeneration in brain and extramedullary haemopoiesis in spleen. H. hypnale venom caused all above histopathological alterations at lower doses compared to the other two.
Conclusion
Hypnale venoms cause similar pathological changes with marked differences in the severity of the toxic effects in vivo. Therefore, differences in the severity of the clinical manifestations could possibly be seen among bite victims of the three Hypnale species.
【 授权许可】
2012 Silva et al.; licensee BioMed Central Ltd.
【 预 览 】
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20150416033926822.pdf | 2277KB | download | |
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Figure 2. | 84KB | Image | download |
Figure 1. | 98KB | Image | download |
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【 参考文献 】
- [1]Kasturiratne A, Pathmeswaran A, Fonseka MMD, Lalloo DG, Brooker S, de Silva HJ: Estimates of disease burden due to land–snake bite in Sri Lankan hospitals. Southeast Asian J Trop Med Public Health 2005, 36:733-740.
- [2]Ariyaratnam CA, Thuraisingam V, Kularatne SAM, Sheriff MHR, Theakston RDG, de Silva A, Warrell DA: Frequent and potentially fatal envenoming by hump–nosed pit vipers (Hypnale hypnale and H. nepa) in Sri Lanka: lack of effective antivenom. Trans R Soc Trop Med Hyg 2008, 102:1120-1126.
- [3]Joseph JK, Simpson ID, Menon NCS, Jose MP, Kulkarni KJ, Raghavendra GB, Warrell DA: First authenticated cases of life–threatening envenoming by the hump–nosed pit viper (Hypnale hypnale) in India. Trans R Soc Trop Med Hyg 2007, 101:85-90.
- [4]Maduwage K, Silva A, Manamendra-Arachchi K, Pethiyagoda R: A taxonomic revision of the South Asian pit viper genus Hypnale (Fitzinger). Zootaxa 2009, 2232:1-28.
- [5]Kularatne SA, Ratnatunga N: Severe systemic effects of Merrem’s hump–nosed viper bite. Ceylon Med J 1999, 44:169-170.
- [6]De Silva A, Wijekoon ASB, Jayasena L, Abeysekara CK, Bao CX, Hutton RA, Warrell DA: Haemostatic dysfunction and acute renal failure following envenoming by Merrem’s hump–nosed viper (Hypnale hypnale) in Sri Lanka: first authenticated case. Trans R Soc Trop Med Hyg 1994, 88:209-212.
- [7]Maduwage K, Kularatne K, Wazil A, Gawarammana I: Coagulopthy, acute kidney injury and death following Hypnale zara envenoming – The first case report from Sri Lanka. Toxicon 2011, 58:641-643.
- [8]Tan CH, Leong PK, Fung SY, Sim SM, Ponnudurai G, Ariaratnam C, Khomvilai S, Sitprija V, Tan NH: Cross neutralization of Hypnale hypnale (hump–nosed pit viper) venom by polyvalent and monovalent Malayan pit viper antivenoms in vitro and in a rodent model. Acta Trop 2011, 117:119-124.
- [9]Tan CH, Sim SM, Gnanathasan CA, Fung SY, Ponnudurai G, Pailoor J, Tan NH: Enzymatic and toxinological activities of Hypnale hypnale (hump-nosed pit viper) venom and its fractionation by ion exchange high performance liquid chromatography. J Venom Anim Toxins 2011, 17:473-485.
- [10]Maduwage K, Hodgson WC, Konstantakopoulos N, O'Leary MA, Gawarammana I, Isbister GK: The in vitro toxicity of venoms from South Asian Hump–nosed pit vipers (Viperidae: Hypnale). J Venom Res 2011, 2:17-23.
- [11]Bradford M: A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976, 72:248-254.
- [12]Howard-Jones NA: ACIOMS ethical code for animal experimentation. WHO Chron 1995, 39:51-56.
- [13]Finney DJ: Probit Analysis. England: Cambridge University Press; 1952.
- [14]Gunatilake M, Jayakody RL, Angunawala P, de Tissera A: Direct nephrotoxic effects produced by venoms of Sri Lankan cobra, Russell’s viper and Hump-nosed viper. Ceylon J Med Sci 2003, 46:61-66.
- [15]Sitprija V: Snakebite nephropathy. Nephrology 2006, 11:442-448.
- [16]Varagunam T, Panabokke RG: Bilateral necrosis of the kidneys following snakebite. Postgrad Med J 1970, 46:449-451.
- [17]Herath N, Wazil A, Kularatne K, Ratnatunga N, Weerakoon K, Badurdeen S, Rajakrishna P, Nanayakkara N, Dharmagunawardane D: Thrombotic microangiopathy and acute kidney injury in hump-nosed viper (Hypnale species) envenoming: A descriptive study in Sri Lanka. Toxicon 2012, 60:61-65.
- [18]Isbister GK: Snakebite doesn't cause disseminated intravascular coagulation: coagulopathy and thrombotic microangiopathy in snake envenoming. Semin Thromb Hemost 2010, 36:444-451.
- [19]Sellahewa KH, Kumararatne MP: Envenomation by the Hump-nosed viper (Hypnale hypnale). Am J Trop Med Hyg 1994, 51:823-825.
- [20]Silveira KS, Boechem NT, Do Nascimento SM, Murakami YL, Barboza AP, Melo PA, Castro P, De Moraes VL: Pulmonary mechanics and lung histology in acute lung injury induced by Bothrops jararaca venom. Resp Physio Neurobiol 2004, 139:167-177.
- [21]Dharmaratne L, Gunawardena U: Generalized bleeding tendency and acute renal failure following Merrem’s Hump-nosed viper bite. J Ceylon Coll Phy 1988–89, 21-22:37-42.
- [22]Barraviera B, Coelho KY, Curi PR, Meira DA: Liver dysfunction in patients bitten by Crotalus durissus terrificus snakes in Botucatu. Rev Inst Med Trop São Paulo 1995, 37:63-69.
- [23]Haschek WM, Rousseaux CG, Wallig MA: Fundamentals of Toxicologic Pathology. 2nd edition. London: Academic press; 2010.
- [24]Lukas G, Brindle SD, Greengard P: The route of absorption of intraperitoneally administered compounds. J Pharmacol Exp Ther 1971, 178:562-564.
- [25]Chippaux JP: Snake venoms and envenomations. Melbourne: Kreiger Publishing Company; 2006.