Action of neuwiedase, a metalloproteinase isolated from Bothrops neuwiedi venom, on skeletal muscle: an ultrastructural and immunocytochemistry study

Abstract

Abstract:The damaging effects of neuwiedase, a non-hemorrhagic snake venom metalloproteinase from P-I class, on gastrocnemius muscle are studied herein. Following neuwiedase injection, ultrastructural alterations were detected early showing disarrangement of skeletal muscle fibers (characterized by discontinuity of Z lines), mitochondrial swelling, and disruption of plasma membrane and basal lamina. Degradation of skeletal muscle and the appearance of an amorphous substance, primarily composed of cellular debris, were noted after 24 hours. The presence of neuwiedase at the injection site (detected by immunocytochemistry) revealed highly specific labeling of myofibril components of damaged myocytes. In addition, proteolysis of muscle proteins assayed through myofibrils extracted from gastrocnemius muscle indicated that neuwiedase provoked degradation of myofibrils, especially myosin. These results suggest that skeletal muscle damage, induced by neuwiedase, is probably due to its proteolytic action on myofibrils, which are responsible for the maintenance of the cellular architecture.

Inhibition by essential oils of Mentha viridis and Mentha pulegium (Lamiaceae) in proteolysis, fibrinogenolysis and coagulation caused by venomous snakes

“…Snake venom proteases can act by breaking on different protein substrates such as components of cell membranes, blood and tissues proteins and those that make up the basal lamina (Markland, 1998;Baldo et al, 2010). Other studies also report the action of metalloproteases and phospholipases on cells and molecules that integrate the hemostatic system (Escalante, Rucavado, Fox, & Gutiérrez, 2011;Bernardoni et al, 2014;Sharon, Trabi, & Richards, 2016), as well as the mechanisms by which these classes of toxins act in the blood coagulation cascade.…”

Caracterização bioquímica e farmacológica da peçonha de Leptodeira annulata (Colubridae, Dipsadinae, Leptodeirini)

“…annulata, junto com as PLA2, é provável que a miotoxicidade tenha sido produzida por essas enzimas. O mecanismo de ação pode incluir a hidrólise de fosfolipídios do sarcolema pelas PLA2 [38], a isquemia local resultante da extensa hemorragia e a ação de enzimas proteolíticas sob as miofibrilas (especialmente a miosina), as quais são responsáveis pela manutenção da arquitetura celular [101,102,107,111].…”

“…Embora a DMH determinada no presente trabalho para a peçonha de L. annulata em pele de rato (95,8 µg) não seja diretamente comparável com os resultados obtidos em camundongos, ela é menor que a DMH de várias peçonhas botrópicas, e.g., B. alternatus 170 µg, B. jararaca 140 µg, B. neuwiedii 210 µg e B. moojeni 150 µg[100]. A inibição da atividade hemorrágica por reagentes quelantes aponta para o envolvimento de SVMPs neste fenômeno, o que também ocorre em peçonhas de outras Colubridae e do gênero Bothrops[17,18,26,27,43,[101][102][103][104][105][106].…”