Protection by Mikania laevigata (guaco) extract against the toxicity of Philodryas olfersii snake venom.
Philodryas olfersii is responsible for most colubrid snakebites in Brazil. In this work, we examined the ability of an ethanolic extract from Mikania laevigata (guaco) leaves to protect against the in vitro neuromuscular activity of P. olfersii venom in mouse phrenic nerve-diaphragm (PND) and chick biventer cervicis (BC) preparations. M. laevigata extract caused moderate twitch-tension facilitation at low concentrations (107.4 ± 6.2% with 20 μl/ml and 118.9 ± 9.3% with 40 μl/ml in PND, and 120.7 ± 7.7% with 40 μl/ml and 114.5 ± 4.4% with 50 μl/ml in BC after 120 min; n = 4-6, mean ± SEM). In PND, the ethanol alone (40 μl/ml, n = 4) did not change the twitch-tension when compared with control. However, in BC, the ethanol produced a higher facilitation when compared to control. At higher concentrations (>50 μl/ml) the extract caused total and reversible blockade in both preparations. Venom (50 μg/ml) caused partial blockade in PND (58.5 ± 12%, n = 4) and almost total blockade in BC (93.5 ± 2.2%, n = 4). Pretreatment of the preparations with extract (40 μl/ml) for 30 min before incubation with venom (50 μg/ml) completely protected PND from neuromuscular blockade and delayed the blockade in BC. The extract alone caused only mild morphological alterations (12.5 ± 0.5% and 10.9 ± 2.3% fiber damage in PND and BC, respectively, compared to 2.3 ± 0.3% and 3 ± 0 in controls; n = 3), with no increase in expression of the inflammatory cytokines TNFα and IFNγ. The ethanol alone also caused slight muscle damage: 4.3 ± 2.4% in PND and 6.7 ± 3.3% in BC (both n = 3) and little or no TNFα and IFNγ expression in both preparations as observed in control. Venom (50 μg/ml) caused 53.5 ± 8.5% and 55.8 ± 4.3% fiber damage in PND and BC, respectively; (n = 3, p < 0.05 vs. controls) and enhanced expression of TNFα and IFNγ. Pretreatment of the preparations with extract protected against venom-induced muscle damage by 80.3 and 60.4 in PND and BC, respectively, and prevented TNFα and IFNγ expression. These results indicate that the M. laevigata extract protected nerve-muscle preparations against the myotoxic, neurotoxic and inflammatory effects of P. olfersii venom.
Departamento de Ciências Fisiológicas, Faculdade das Ciências Médicas e da Saúde, Pontifícia Universidade Católica de São Paulo (PUC/SP), Praça José Ermírio de Moraes 290, Sorocaba 18030-095, SP, Brazil. cassia_collaco@hotmail.com
Rita de Cássia O
Rde C
Collaço
José Carlos
JC
Cogo
Léa
L
Rodrigues-Simioni
Thalita
T
Rocha
Yoko
Y
Oshima-Franco
Priscila
P
Randazzo-Moura
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D002645:Chickens; D017812:Colubridae / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects; D008297:Male; D051379:Mice; D035742:Mikania / Q000737:chemistry*; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D019148:Neuromuscular Blockade; D009466:Neuromuscular Blocking Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009469:Neuromuscular Junction / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D012910:Snake Venoms / Q000037:antagonists & inhibitors / Q000633:toxicity*
D000931:Antidotes; D009466:Neuromuscular Blocking Agents; D018696:Neuroprotective Agents; D010936:Plant Extracts; D012910:Snake Venoms