Snake envenoming is an important public health problem around the world, particularly in tropics. Beyond deaths, morbidity induced by
snake venoms, such as
myotoxicity, is of pivotal consequence to population. Bothrops jararacussu is the main venomous snake in southeast region of Brazil, and particularly presents strong myotoxic effect. The only available
therapy, antibothropic
antivenom, poorly affects
venom-induced
myotoxicity. The aim of this study is to assess the ability of
fucosylated chondroitin sulfate (fucCS), a
glycosaminoglycan with
anticoagulant and antithrombotic properties, and its derivatives to inhibit toxic activities of B. jararacussu crude
venom and its isolated toxins, named bothropstoxins (
BthTX-I and
BthTX-II). The in vitro myotoxic activities induced by crude
venom, by
BthTX-I alone and by toxins together were abolished by fucCS. Carboxyl reduction (fucCS-CR) kept this ability whereas defucosilation (defucCS) abrogates myoprotection. We observed the same pattern in the response of these
polysaccharides in antagonizing the increase in plasma
creatine kinase (CK) levels, the reduction of skeletal muscle CK content and the rise of
myeloperoxidase (MPO) activity induced by crude
venom and isolated toxins. FucCS inhibited edematogenic activity and partially prevented the reduction of total leukocytes in blood when pre-incubated with crude
venom. Furthermore, the
venom procoagulant effect was completely antagonized by increasing concentrations of fucCS, although this polyanion could stop neither the tail
bleeding nor the skin
hemorrhage induced by
Bothrops jararaca venom. The B. jararacussu
phospholipase,
hyaluronidase, proteolytic and
collagenase activities were inhibited in vitro. The results suggest that fucCS could be able to interact with both toxins, and it is able to inhibit
BthTX-II phospholipase activity. Light microscopy of extensor digitorum longus muscle (EDL) muscle showed myoprotection by fucCS, once necrotic areas,
edema and inflammatory cells were all decreased as compared to
venom injection alone. Altogether, data show that fucCS was able to inhibit
myotoxicity and
inflammation induced by B. jararacussu
venom and its
phospholipase toxins,
BthTX-I and
BthTX-II. Thus,
fucosylated chondroitin sulfate is a new polyanion with potential to be used as an adjuvant in the treatment of
snakebites in the future.