The Triterpenoid Betulin Protects against the Neuromuscular Effects ofBothrops jararacussuSnake VenomIn Vivo

Abstract

We confirmed the ability of the triterpenoid betulin to protect against neurotoxicity caused byBothrops jararacussusnake venomin vitroin mouse isolated phrenic nerve-diaphragm (PND) preparations and examined its capability ofin vivoprotection 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 ofB. jararacussuvenomin vivoand could be a useful complementary measure to antivenom therapy for treating snakebite.