Effects of Mikania glomerata Leaf Extract on Experimental Bothropoides jararaca Envenomation in Wistar Rats
DOI:
https://doi.org/10.22456/1679-9216.80252Keywords:
anti-venom, bothropic, ophidic, snakebite.Abstract
Background: Bothropic envenomation represents the most common ophidic accident worldwide, compared to other snakebites of medical interest. Bothropic venom has proteolytic, vasculotoxic, clotting and/or hemorrhagic actions in animals and humans. Mikania glomerata is a plant found in the Brazilian Atlantic Forest with interesting medical properties that may be useful in ameliorating the effects of ophidic venom, and thus, improving response and outcome. Although Mikania is known to act through inhibition of cytolysins in the venom, there is a lack of consistent research data. The aim of this study was to evaluate the effect of M. glomerata in bothropic envenomation treatment.
Materials, Methods & Results: Clinical, hematological, biochemical, and histopathological evaluations were performed following Bothropoides jararaca experimental envenomation in three groups of 18 Wistar rats each. Group VS was inoculated in the pelvic limb via intramuscular injection of bothropic venom and received specific anti-venom serum via intraperitoneal injection. Group VSM was similarly inoculated; it received anti-venom serum and a 10% aqueous extract of the Mikania glomerata plant orally. Group C was the control group and received saline solution alone. Evaluations were performed at 0.5 h (M1), 6 h (M2), and 24 h (M3) after venom inoculation. Animals from both inoculated groups (VS and VSM) showed significant clinical alterations (P < 0.05) manifested as discomfort, uneasiness, pain, and severe edema compared to control animals. Animals from inoculated groups also exhibited statistically significant leukocytosis with neutrophilia, and elevation of blood urea nitrogen and creatine kinase until 6 h after inoculation (P < 0.05 compared to control animals). An acute drop in body temperature was observed 6 h after inoculation (P < 0.05). High levels of creatinine were observed at 6 and 24 h, and plasma protein reduction at almost all evaluation time points (P < 0.05) in both groups compared to that in control. Histopathological evaluation of venom-inoculated animals (groups VS and VSM) showed significant renal hydropic degeneration, acute tubular necrosis, congestion, and hemorrhage (P < 0.05 compared to control). In contrast, animals administered plant extract in addition to anti-venom (group VSM) showed milder muscular fiber regeneration and absence of hemorrhage in the inoculated limb, compared to those that received anti-venom alone (group VS). Overall, there were no statistically significant differences between the inoculated groups (P > 0.05) in terms of edema reduction, pain relief, hematological, biochemical, or histopathological alterations.
Discussion: Clinical envenomation symptoms can be explained based on previous reports of bothropic events, where cytolysins such as hyaluronidase, phospholipase A2, and esterases are associated with alterations in cell membrane permeability and release of vasoactive agents. Rhabdomyolysis and muscular necrosis are the main causes of muscular and renal alterations in inoculated groups. M. glomerata extract is known to exert its inhibitory effects on vasoactive and lytic compounds responsible for muscular necrosis. However, some authors have reported only partial effectiveness of Mikania in inactivating bothropic toxins, in contrast with its greater inhibitory action on crotalic venoms. Further studies are necessary for detailed exploration of the properties of Mikania glomerata extract in order to integrate it into supportive measures for snakebite treatments in tropical and subtropical countries.
Downloads
References
Albuquerque P.L.M.M., Jacinto C.N., Silva Junior G.B., Lima J.B., Veras M.S. & Daher E.F. 2013. Acute kidney injury caused by Crotalus and Bothrops snake venom: a review of epidemiology, clinical manifestations and treatment. Revista do Instituto de Medicina Tropical de São Paulo. 55(5): 295-301.
Collaço R.C.O., Cogo J.C., Rodrigues-Simioni L., Rocha T., Oshima-Franco Y. & Randazzo-Moura P. 2012. Protection by Mikania laevigata (Guaco) extract against the toxicity of Philodryas olfersii snake venom. Toxicon. 60(4): 614-622.
Conselho Nacional de Controle de Experimentação Animal (CONCEA). 2013. Resolução Normativa 13 de 2013. Brasília: Diário Oficial da União. 11p.
Ferreira Júnior R.S. & Barravieira B. 2004. Management of venomous snakebites in dogs and cats in Brazil. Journal of Venomous Animals and Toxins Including Tropical Diseases. 10(1): 112-132.
Floriano R.S., Nogueira R.M.B., Sakate M., Laposy C.B., Motta Y.P. & Sangiorgio F. 2009. Effect of Mikania glomerata (Asteraceae) leaf extract combined with anti-venom serum on experimental Crotalus durissus (Squamata: Viperidae) envenomation in rats. Revista de Biologia Tropical. 57(4): 929-940.
Jain N.C. 1993. Essentials of Veterinary Hematology. Philadelphia: Wiley-Blackwell, 417p.
Kaneko J.J., Harvey J.W. & Bruss M.L. 2008. Clinical Biochemistry of Domestic Animals. 6th edn. Burlington: Elsevier, 916p.
Lenchner I., Aroch I., Segev G., Kelmer E. & Bruchim Y. 2014. A retrospective evaluation of Vipera palaestinae envenomation in 18 cats: (2006-2011). Journal of Veterinary Emergency and Critical Care. 24(4): 437-443.
Maiorano V.A., Marcussi S., Daher M.A.F., Oliveira C.Z., Couto L.B., Gomes O.A., França S.C., Soares A.M. & Pereira P.S. 2005. Antiophidian properties of the aqueous extract of Mikania glomerata. Journal of Ethnopharmacology. 102(3): 364-470.
Mourão V.B., Giraldi G.M., Neves L.M.G., Gaspi F.O.G., Rodrigues R.A.F., Alves A.A., Esquisatto M.A.M., Mazzi M.V., Mendonça F.A.S. & Santos G.M.T. 2014. Anti-hemorrhagic effect of hydro-alcoholic extract of the leaves of Mikania glomerata in lesions induced by Bothrops jararaca venom in rats. Acta Cirúrgica Brasileira. 29(1): 30-37.
Nogueira R.M.B. & Sakate M. 2006. Clinical and hematological alterations in dogs during experimental envenomation with Crotalus durissus terrificus venom and treated with antiophidic serum. Journal of Venomous Animals and Toxins Including Tropical Diseases. 12(2): 285-296.
Nogueira R.M.B. 2011. Intoxicação Por Animais Peçonhentos. In: Barilli R.M.N. & Andrade S.F. (Eds). Manual de Toxicologia Veterinária. São Paulo: Roca, pp.295-313.
Ribeiro L.A. & Jorge M.T. 1997. Acidente por serpentes do gênero Bothrops: série de 3139 casos. Revista Da Sociedade Brasileira de Medicina Tropical. 30(6): 475-480.
Rufatto L.C., Gower A., Schwambach J. & Moura S. 2012. Genus Mikania: chemical composition and phytotherapeutical activity. Brazilian Journal of Pharmacognosy. 22(6): 1384-1403.
Sakate M., Nogueira R.M.B. & Motta Y.P.M. 2015. Animais Peçonhentos. In: Jericó M.M., Andrade Neto J.P. & Kogika M.M. (Eds). Tratado de Medicina Interna de Cães e Gatos. Rio de Janeiro: Roca, pp.664-677.
Sangiorgio F., Sakate M., Nogueira R.M.B. & Tostes R.A. 2008. Histopathological evaluation in experimental envenomation of dogs with Crotalus durissus terrificus Venom. Journal of Venomous Animals and Toxins Including Tropical Diseases. 14(1): 82-99.
Sgrignolli L.R., Mendes G.E.F., Carlos C.P. & Burdmann E.A. 2011. Acute kidney injury caused by Bothrops snake venom. Nephron - Clinical Practice. 119(2): 131-137.
Tolosa E.M.C., Rodrigues C.J., Behmer O.A. & Freitas Neto A.G. 2003. Manual de Técnicas para Histologia Normal e Patológica. São Paulo: Manole, 341p.
Vásquez J., Alarcón J.C., Jiménez S.L., Jaramillo G.I., Gómez-Betancur I.C., Rey-Suárez P.J., Jaramillo K.M., Muñoz D.C., Marín D.M. & Romero J.O. 2015. Main plants used in traditional medicine for the treatment of snake bites in the regions of the department of Antioquia, Colombia. Journal of Ethnopharmacology. 170(1): 158-166.
Published
How to Cite
Issue
Section
License
This journal provides open access to all of its content on the principle that making research freely available to the public supports a greater global exchange of knowledge. Such access is associated with increased readership and increased citation of an author's work. For more information on this approach, see the Public Knowledge Project and Directory of Open Access Journals.
We define open access journals as journals that use a funding model that does not charge readers or their institutions for access. From the BOAI definition of "open access" we take the right of users to "read, download, copy, distribute, print, search, or link to the full texts of these articles" as mandatory for a journal to be included in the directory.
La Red y Portal Iberoamericano de Revistas Científicas de Veterinaria de Libre Acceso reúne a las principales publicaciones científicas editadas en España, Portugal, Latino América y otros países del ámbito latino