Jararaca (Bothrops jararaca)
Jararaca - Bothrops jararaca |
The snakes from genus Bothrops are divided into 21 species
that have a large distribution in Brazil . They are responsible for
90% of accidents caused by snakes bites and their venoms have a large variety
of complex toxins that act on the hemostatic system. In a general way, these
toxins can be separated in groups based on their activity in the hemostatic
system. Therefore, there are toxins that act in the coagulation process; there
are those that act in the plaquetes and cause lesions in the vascular system
resulting in a hemorrhagic effect (ROSENFELD, 1971). Based on these facts, the Bothrops
venom is largely studied, especially the toxins that can have therapeutic
applications for various snake bites.
Local pain, edema, local and systemic
hemorrhages, and blood coagulation disturbances are usual symptoms
observed in accidents inflicted by Bothrops snakes (ROSENFELD,
1971). In fact, edema is one of the local effects of Bothrops
envenomation less efficiently neutralized by serum therapy (CARDOSO
et al., 1993). The rapid manifestation of edema and its modulation by
endogenous mediators decrease the efficacy of serum therapy (FRANCA
et al, 2003). Once serum therapy has a low efficacy to treat the
local edema of patients bitten by Bothrops snakes, other
therapies have been investigated.
Damage of Jararaca bitten |
Myotoxins and metalloproteinases
present in Bothrops venoms can induce liberation of endogenous
inflammatory mediators from affected tissues (TEIXEIRA et al., 2003;
BJARNASON and FOX, 1994). Thus, associating anti-inflammatory drugs,
such as dexamethasone or indomethacin, with antivenom should be a
rational alternative to treat the local reaction provoked by Bothrops
venoms. Studying this idea, many tests were made to get into the
conclusion that the efficiency of serum therapy was improved when
antivenom was administered in combination with dexamethasone or
indomethacin (ARAUJO et al., 2007). Preliminary results point out to
the efficacy of treatment of patients accidentally envenomed by
Bothrops snakes with an association of dexamethasone and
serum, especially for reducing edema in the first day after
envenomation (SUSAKI et al., 2005).
Trombin-like: serinoproteases
that convert fibrinogen into fibrin non-stable. This makes with the
clots be not stable.
Pro-coagulant: serinoproteases
that activate the coagulate cascade. The most important are: Factor
X activator, that convert factor X into Xa; Protrombim
activator, that converts protrombin into trombones independently
of phospholipids and factor Va and Trombocitin, activate
factors V, VIII and XIII.
Anticoagulants: the most
important are: Protein C activator, the protein C activation
leads to the inhibition of factors Va and VIIIa; Botrojaracin,
trombone inhibitor; Botrocetins, inhibitors of factor Xa, IX
and X and Jararafibrases, fibrin and fibrinogen degradation.
Pro-aggregating platelets:
proteases that activate platelets due to the secretion of ADP.
Anti-aggregating platelets:
prevents that the platelets binds in the surface of the damaged
tissue, blocking the integrins.
Metaloproteases: enzymes that
degrade many kinds of protein and can cause hemorrhage.
Studies indicating how Bothrops venom affects the offspring
were developed in mice. As a result of envenomation the researchers observed
that the offspring presented a high incidence of skeletal anomalies such as
vertebrae anomalies, sternebrae anomalies and incomplete skull ossification
(BERNARDI et al., 2011).
Bothrops jarara |
Other kinds of studies that
have being developed utilizing the Bothrops venom are those that use the
toxins for medical treatments, such the drug Captopril first developed from the
jararaca venoms to treat hypertension. Pyroglutamyl proline-rich oligopeptides,
present in the venom of the pit viper Bothrops jararaca (Bj-PROs),
are the first described naturally occurring inhibitors of the angio- tensin
I-converting enzyme (ACE), which is a new class of therapeutic agents for the
treatment of hypertension (SMITH and VANE, 2003). Studies about the Bj-PRO-10c,
a oligopeptide from Bothrops jararaca, has shown that this oligopeptide
evoked changes in arterial blood pressure that were followed by a significant
reduction of heart rate (FERREIRA et al, 1970a and 1970b). Taking the results
presented in the literature, the mechanism of action of Bj-PRO-10c appears to provide evidence that Bj-PRO-10c
induces transient increases of free intracellular calcium concentration in
neuronal cells through a mechanism by activation of a yet unknown Gi/o-protein coupled
receptor and promotes release of neurotransmitters in neuronal cells, namely
GABA and glutamate, which may contribute to central cardiovascular effects
exerted by Bj-PRO-10c (IANZER et al., 2007; LAMEU et al., 2010).
Botrhops jararaca attack
References:
Araujo, S. D., Souza A., Nunes, F.P.B. and Goncalves, L.R.C. Effect of dexamethasone associated with serum theraphy on treatment of Bothrops jararaca venom-induced paw edema in mice. Inflamm. Res. 56, 2007.
Bernardi, M. M., Kirsten, T. B., Manetta, P. R., Harb,
S.F., Macrini D.J. And Cury, Y. Maternal exposure to Bothrops
jararaca snake venom: effects in mice offsprings. J Health Sci Inst.
2011.
Bjarnason JB, Fox JW. Hemorrhagic metalloproteinases from snake venoms. Pharmacol. Ther. 1994.
Cardoso JL, Fan HW, França FO, Jorge MT, Leite RP, Nishioka SA et al. Rando- mized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops Jararaca) in São Paulo. Q J Med., 86, 1993.
Ferreira SH, Greene LH, Alabaster VA,
Bakhle YS, Vane JR. Activity of various fractions of bradykinin
potentiating factor against angiotensin I converting enzyme. Nature,
1970.
Ferreira SH, Bartelt DC, Greene LJ.
Isolation of bradykinin-potentiating peptides from Bothrops
jararaca venom. Biochemistry, 1970.
França FOS, Málaque CMS. Acidente
botrópico. In: Cardoso JLC, França FO, Fan HW, Málaque CMS,
Haddad Jr V (eds.), Animais Peçonhentos no Brasil: Biologia,
clínica e terapêutica dos aciden- tes. São Paulo: Sarvier,
2003.
Ianzer D, Santos RA, Etelvino GM,
Xavier CH, de Almeida Santos J, Mendes EP, Machado LT, Prezoto BC,
Dive V, de Camargo AC. Do the cardiovascular effects of
angiotensin-converting enzyme (ACE) I involve ACE-independent
mechanisms? New insights from proline-rich peptides of Bothrops
jararaca. J Pharmacol Exp Ther, 2007.
Lameu, C., Hayashi, M. A., Guerreiro,
J. R., Oliveira, E. F., Lebrun, I., Pontieri, V., Morais, K. L. P.,
Camargo, A. C. M. and Ulrich H. The Central Nervous System as Target
for Antihypertensive Actions of a Proline-rich Peptide from Bothrops
jararaca Venom. Cytrometry Part A, 2010.
Rosenfeld G. Symptomathology, pathology and treatment of snakes bites in South America. In: Bucherl W, Buckley E,Editors. Venomous animals and their venoms. New York: Academic Press; 1971.
Smith CG, Vane JR. The discovery of
captopril. FASEB J, 2003.
Susaki TT, Fan HW, Málaque CMS,
Medeiros CR, Cardoso JLC, Ferrari RA et al. Effect of dexamethasone
therapy on local edema after Bothrops accidents. Mem.
Instituto Butantan 2005.
Teixeira CFP, Landucci ECT, Antunes E,
Chacur M, Cury Y. In- flammatory effects of snake venom myotoxic
phospholipase A2. Toxicon, 2003.