Title:Histological and Ultrastructural Analyses of Muscle Damage Induced by a Myotoxin Isolated from Bothrops alternatus Snake Venom
VOLUME: 20 ISSUE: 2
Author(s):Carla Cristine Neves Mamede, Mayara Ribeiro de Queiroz, Kelly Cortes Fonseca, Nadia Cristina Gomes de Morais, Saulo Antonio Gomes Filho, Marcelo Emilio Beletti, Leonilda Stanziola and Fabio de Oliveira
Affiliation:Instituto de Ciencias Biomedicas/ Universidade Federal de Uberlandia - Av. Para 1720 - Bloco 2A - 2º andar - Campus Umuarama- Uberlandia - MG - CEP 38400-902.
Keywords:Bothrops alternatus, histopathology, myotoxin, myonecrosis, skeletal muscle, ultrastructural alterations
Abstract:Muscular necrosis is a serious consequence of Bothrops snake bites that may lead to permanent loss of tissue or
function. Myonecrosis may be due to injury to blood vessels, destabilization and/or rupture of plasma membrane, and inflammatory
mechanisms triggered by different proteins from the snake venom. In this work we describe the isolation and
partial functional characterization of a myotoxin from B. alternatus snake venom. The myotoxin was isolated by a combination
of ion exchange and gel filtration chromatography and displayed a molecular weight of approximately 15,000, as
estimated by SDS–PAGE under reducing conditions. In non-reducing conditions a protein band of approximately 25,000
was also observed, suggesting that its native form is a homodimer. The myotoxin induced myonecrosis, but had no proteolytic
and phospholipase A2 activities. The myotoxic activity was assessed on the basis of the histological and ultrastructural
alterations induced by the toxin in the gastrocnemius skeletal muscle of Swiss mice. The toxin led to a series of drastic
degenerative events characterized by extensive cellular destruction, loss of the arrangements of skeletal fibers, intense
infiltration of inflammatory cells, fatty degeneration and hemorrhage. Electron microscopy analyses revealed that the
myotoxin caused cell swelling, mitochondrial alterations and dilation of the sarcoplasmic reticulum, but did not affect the
integrity of the muscle cell membranes. The myonecrosis caused by this toxin was related to the perturbation in the membrane
permeability, intracellular alterations and inflammatory reaction.
