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Evid Based Complement Alternat Med
2015 Jan 01;2015:939523. doi: 10.1155/2015/939523.
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The Triterpenoid Betulin Protects against the Neuromuscular Effects of Bothrops jararacussu Snake Venom In Vivo.
Ferraz MC
,
de Oliveira JL
,
de Oliveira Junior JR
,
Cogo JC
,
Dos Santos MG
,
Franco LM
,
Puebla P
,
Ferraz HO
,
Ferraz HG
,
da Rocha MM
,
Hyslop S
,
San Feliciano A
,
Oshima-Franco Y
.
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We confirmed the ability of the triterpenoid betulin to protect against neurotoxicity caused by Bothrops jararacussu snake venom in vitro in mouse isolated phrenic nerve-diaphragm (PND) preparations and examined its capability of in vivo protection using the rat external popliteal/sciatic nerve-tibialis anterior (EPSTA) preparation. Venom caused complete, irreversible blockade in PND (40 μg/mL), but only partial blockade (~30%) in EPSTA (3.6 mg/kg, i.m.) after 120 min. In PND, preincubation of venom with commercial bothropic antivenom (CBA) attenuated the venom-induced blockade, and, in EPSTA, CBA given i.v. 15 min after venom also attenuated the blockade (by ~70% in both preparations). Preincubation of venom with betulin (200 μg/mL) markedly attenuated the venom-induced blockade in PND; similarly, a single dose of betulin (20 mg, i.p., 15 min after venom) virtually abolished the venom-induced decrease in contractility. Plasma creatine kinase activity was significantly elevated 120 min after venom injection in the EPSTA but was attenuated by CBA and betulin. These results indicate that betulin given i.p. has a similar efficacy as CBA given i.v. in attenuating the neuromuscular effects of B. jararacussu venom in vivo and could be a useful complementary measure to antivenom therapy for treating snakebite.
Figure 3. Contractile responses of rat indirectly stimulated EPSTA preparations after treatment with saline (a), CBA (b), and PEG 400 (c). Saline and PEG 400 were injected i.m. in the left hind limb, whereas CBA was injected i.v. The recordings are representative of four experiments for the saline and CBA treatments; only one experiment was done with PEG 400 since we have shown elsewhere that this reagent is compatible with biological preparations [38]. Substances were injected at the arrow. Tension scale bar = 20 g/cm.
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