A study of the myotoxicity of bothropstoxin-i using manganese in mouse phrenic nerve-diaohragm and extensor digitorum longus preparations
Braz. j. morphol. sci
; 23(2): 237-246, Apr.-June 2006. ilus
Article
in En
| LILACS
| ID: lil-468065
Responsible library:
BR734.1
ABSTRACT
Bothropstoxin-I (BthTX-I) from Bothrops jararacussu snake venom has a predominantly postsynaptic action that is responsible for this toxin´s myotoxicity. However, BthTX-I also has a presynaptic action that is counteracted by Mn2+, a reversible neuromuscular blocker that acts predominantly presynaptically. In this work, we used two nerve-muscle preparations (mouse phrenic nerve-diaphragm - PND and extensor digitorum longus - EDL) to investigate the ability of Mn2+ to protect against the myotoxicity of BthTX-I. The preparations were incubated with Tyrode solution (control), BthTX-I, or Mn2+ alone. BthTX-I (1.4 µM) produced irreversible blockade in both preparations, whereas the blockade by Mn2+ (0.9 mM) was total and reversible in PND but just partially reversible in EDL. Pretreating the preparations with Mn2+ resulted in 100% and 80% protection against BthTX-I-induced blockade, respectively. However, when Mn2+ (0.9 or 1.8 mM) and BthTX-I (1.4 µM) were co-incubated for 30 min before testing, the blockade was faster and sustained. Washing the preparations resulted in complete, sustained recovery in those exposed to 1.8 mM Mn2+ but not to 0.9 mM Mn2+. Morphological analysis showed that the extent of fiber damage by BthTXI (1.4 µM) was 82% (PND) and 68.5% (EDL), and that Mn2+ (0.9 mM) afforded 40% protection in both preparations and reduced the increase in muscle fiber cross-sectional area by 20% and 15%, respectively, compared to BthTX-I alone. Mn2+ (0.9 mM) significantly attenuated the release of creatine kinase by BthTXI. The low creatine kinase activity resulted from a protective action of Mn2+ on the sarcolemma and from direct inactivation of the released enzyme. These results show that Mn2+ prevents membrane disruption by BthTX-I and can protect against the myotoxicity and neurotoxicity caused by this toxin.
Full text:
1
Collection:
01-internacional
Database:
LILACS
Main subject:
Snake Venoms
/
Antivenins
/
Crotalid Venoms
/
Manganese
/
Neuromuscular Junction
Limits:
Animals
Language:
En
Journal:
Braz. j. morphol. sci
/
Brazilian journal of morphological sciences
/
Rev. bras. ciênc. morfol
/
Revista brasileira de ciências morfológicas
Journal subject:
ANATOMIA
Year:
2006
Document type:
Article
Affiliation country:
Brazil
Country of publication:
Brazil