Influence of phospholipasic inhibition on neuromuscular activity of Bothrops fonsecai snake venom

被引:4
|
作者
Schezaro-Ramos, Raphael [1 ]
Collaco, Rita de Cassia O. [1 ]
Randazzo-Moura, Priscila [2 ]
Rocha, Thalita [3 ]
Cogo, Jose Carlos [4 ]
Rodrigues-Simioni, Lea [1 ]
机构
[1] Univ Estadual Campinas UNICAMP, Fac Ciencias Med, Dept Farmacol, Rua Tessalia Vieira Camatgo 126, BR-13083887 Campinas, SP, Brazil
[2] PUC SP, Fac Ciencias Med & Saude, Jardim Fac, Praca Dr Jose Ermirio de Moraes 290, BR-18030095 Sorocaba, SP, Brazil
[3] Univ Sao Francisco Univ USF, Lab Multidisciplinar Pesquisa, Ave Sao Francisco Assis 218, BR-12916900 Braganca Paulista, SP, Brazil
[4] Univ Vale Paraiba UNIVAP, Ctr Estudos Nat, Ave Shishima Hifumi 2911, BR-12240000 Sao Jose Dos Campos, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
Snake venom; Bothrops fonsecai; Phospholipase A(2); Neuromuscular activity; Myotoxicity; FOREST VIPER VENOM; 2 MYOTOXIC PHOSPHOLIPASES-A(2); BETA-BUNGAROTOXIN; PRESYNAPTIC ACTION; FIBRIN(OGEN)OLYTIC METALLOPROTEASE; FUNCTIONAL-CHARACTERIZATION; PHARMACOLOGICAL-PROPERTIES; TRANSMITTER RELEASE; MUSCLE NECROSIS; A(2);
D O I
10.1016/j.toxicon.2017.02.027
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Bothrops fonsecai (B. fonsecai), a pitviper endemic to southeastern Brazil, has a venom mainly composed by snake venom phospholipases (PLA(2)) and metalloproteases, compounds that could interfere with neuromuscular junction in vitro. In this work, we investigated the role of PLA(2) in the myotoxicity and neuromuscular blockade caused by B. fonsecai venom using different procedures frequently associated with PLA(2) activity inhibition: 24 degrees C bath temperature, Ca2+-Sr2+ replacement and chemical modification with p-bromophenacyl bromide (p-BPB). Mice extensor digitorum longus preparations (EDL) were incubated with usual or modified Tyrode solution (prepared with Ca2+-or Sr2+ respectively) at 24 degrees C or 37 degrees C (as controls) and in addition of B. fonsecai venom (100 jig/mL) alone or after its incubation with buffer (24 h, 23 degrees C) on the absence (alkylation control) and presence of p-BPB; all muscle were processed for histological analysis. The PLA(2), proteolytic and amidolytic activities under the same conditions (24 degrees C or 37 degrees C, Ca2+-Sr2+ replacement, absence or presence p-BPB) were also assessed. The B. fonsecai venom caused total neuromuscular blockade after 100 min of incubation, in Ca2+ Tyrode solution at 37 degrees C (usual conditions); on Sr2+ Tyrode solution (37 degrees C) the twitch height were 31.7 +/- 7.4% of basal, and at 24 degrees C (Ca2+ Tyrode solution) were 53.6 +/- 7.0% of basal. The alkylation of PLA(2) with p-BPB promoted a great blockade decrease at 100 min of incubation (88.7 +/- 5.7% of basal), but it was also observed on alkylation control preparations (66.2 +/- 6.6%). The venom produced 50% of blockade at 40.5 +/- 5.9 min, in Ca2+ Tyrode solution at 37 degrees C. The protocols delayed the time for 50% blockade: 105.7 +/- 7.1 min (at 24 degrees C, in Ca2+-Tyrode solution) and 71.1 +/- 9.0 min (at 37 degrees C. in Sr2+ Tyrode solution). Regarding p-BPB incubation and alkylation control preparations, 50% of blockade was not reached during the 120 min of venom incubation. Regarding to enzymatic activities, the 24 degrees C protocol reduced not only PLA(2) (to 62.3%) but also proteolytic (52.3%) and amidolytic (73.4%) activities, as well as observed on p-BPB alkylation protocol which markedly inhibited all enzymes (<10%). The alkylation control promoted the same proteolytic and amidolytic inhibition but no reduction of PLA(2) activity; Ca2+-Sr2+ replacement reduced only the PLA(2) activity (to 15.3%). We observed a strict relation between the inhibition of PLA(2) activity and the myotoxicity. On the other hand, this relation was not observed with neuromuscular blockade, suggesting that blockade and muscle damage may not be strictly related. It suggests that the neuromuscular blockade may be induced by non-catalytic PLA(2) or other venom components, such as metalloproteinases. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:35 / 43
页数:9
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