Abstract
Background: In Brazil, the Bothrops genus accounts for 87% of registered snakebites, which are characterized by hemorrhage, tissue necrosis, hemostatic disturbances, and death. The treatment recommended by governments is the administration of specific antivenoms. Although antivenom efficiently prevents venom-induced lethality, it has limited efficacy in terms of preventing local tissue damage. Thus, researchers are seeking alternative therapies able to inhibit the main toxic effects of venoms, without compromising safety.
Objective: The study aimed to test the ability of aqueous extracts of leaves, stems, and fruits of the plant Clusia fluminensis to neutralize some toxic effects induced by the venoms of Bothrops jararaca and Bothrops jararacussu. Methods: The plant extracts were incubated with venoms for 30 min. at 25 °C, and then in vitro (coagulant and proteolytic) and in vivo (hemorrhagic, myotoxic, and edematogenic) activities were evaluated. In addition, the extracts were administered to animals (by oral, intravenous or subcutaneous routes) before or after the injection of venom samples, and then hemorrhage and edema assays were performed. In addition, a gel solution of the fruit extract was produced and tested in terms of reducing hemorrhage effects. A chemical prospection was performed to identify the main classes of compounds present in the extracts. Results: All the extracts inhibited the activities of the two venoms, regardless of the experimental protocol or route of administration of the extracts. Moreover, the gel of the fruit extract inhibited the venom-induced-hemorrhage. The extracts comprised of tannins, flavonoids, saponins, steroids, and terpenoids. Conclusion: Antivenom properties of C. fluminensis extracts deserve further investigation in order to gain detailed knowledge regarding the neutralization profile of these extracts.Keywords: Antivenom, Snake, Bothrops jararaca, Bothrops jararacussu, Plant, Clusia fluminensis, Neutralization.
Graphical Abstract
[http://dx.doi.org/10.1016/j.thromres.2013.09.031] [PMID: 24125598]
[http://dx.doi.org/10.1371/journal.pmed.0050218] [PMID: 18986210]
[http://dx.doi.org/10.1186/s40409-017-0105-z] [PMID: 28293253]
[http://dx.doi.org/10.1590/S0036-46652003000600009]
[http://dx.doi.org/10.1016/j.toxicon.2008.03.018] [PMID: 18471839]
[http://dx.doi.org/10.3109/15569549509019469]
[http://dx.doi.org/10.1016/S0300-9084(00)01163-9] [PMID: 11086214]
[http://dx.doi.org/10.1016/S0041-0101(02)00156-3] [PMID: 12368112]
[PMID: 2804475]
[http://dx.doi.org/10.4269/ajtmh.1999.61.698] [PMID: 10586897]
[http://dx.doi.org/10.3390/molecules14031072] [PMID: 19305361]
[http://dx.doi.org/10.1016/S0031-9422(00)00229-6] [PMID: 11130675]
[http://dx.doi.org/10.1016/j.toxicon.2018.11.289] [PMID: 30447274]
[http://dx.doi.org/10.3390/molecules21101350] [PMID: 27727185]
[http://dx.doi.org/10.1590/S0102-33062002000200009]
[http://dx.doi.org/10.1016/S0003-9861(78)80015-0] [PMID: 28087]
[http://dx.doi.org/10.1016/j.jep.2008.12.009]
[PMID: 10883329]
[http://dx.doi.org/10.1016/0006-2952(94)90525-8] [PMID: 8185661]
[http://dx.doi.org/10.1590/0001-3765201520140564]
[http://dx.doi.org/10.1590/S0100-40422012001100035]
[http://dx.doi.org/10.1002/mabi.201200017] [PMID: 22648985]
[http://dx.doi.org/10.1055/s-0038-1665414] [PMID: 9408022]
[http://dx.doi.org/10.1016/0041-0101(88)90140-7] [PMID: 3347934]
[http://dx.doi.org/10.7883/yoken1952.13.43] [PMID: 13853435]
[http://dx.doi.org/10.1590/S1415-790X2009000100006]
[http://dx.doi.org/10.1371/journal.pntd.0000569] [PMID: 20027216]
[http://dx.doi.org/10.1007/s10126-016-9722-8] [PMID: 27888371]
[http://dx.doi.org/10.1016/j.biologicals.2011.02.005] [PMID: 21429763]
[http://dx.doi.org/10.1016/S0041-0101(02)00104-6] [PMID: 12165312]
[http://dx.doi.org/10.1016/S0041-0101(02)00156-3] [PMID: 12368112]
[http://dx.doi.org/10.1016/j.jep.2009.04.005] [PMID: 19477609]
[http://dx.doi.org/10.6026/97320630003100] [PMID: 19238245]
[PMID: 24660453]
[http://dx.doi.org/10.1016/j.toxicon.2012.09.004] [PMID: 23000249]
[http://dx.doi.org/10.1016/j.jep.2012.10.033] [PMID: 23123799]
[http://dx.doi.org/10.1016/S0140-6736(09)61159-4] [PMID: 20109867]
[http://dx.doi.org/10.1016/j.ejmech.2008.09.018] [PMID: 18995931]
[http://dx.doi.org/10.1016/j.bjp.2016.08.004]
[http://dx.doi.org/10.1016/S1388-1981(00)00105-0] [PMID: 11080672]
[http://dx.doi.org/10.1016/S0305-0491(00)00237-6] [PMID: 11126749]
[http://dx.doi.org/10.1016/S0006-2952(96)00773-3] [PMID: 9113093]
[http://dx.doi.org/10.1590/S0100-40422012001100035]
[PMID: 10883329]
[http://dx.doi.org/10.3831/KPI.2017.20.020] [PMID: 30087793]
[http://dx.doi.org/10.2174/092986705774370655] [PMID: 16248818]
[http://dx.doi.org/10.1590/S1678-91992010000200012]
[http://dx.doi.org/10.5216/ree.v10.46799]
[http://dx.doi.org/10.1016/j.toxicon.2009.03.015] [PMID: 19324064]