A potential new treatment for preventing tissue damage from saw-scaled viper venom is presented in Nature Communications this week. The paper also provides insight into the mechanisms underlying viper venom-induced tissue destruction in mice.
Approximately 5.5 million snakebites - responsible for 0.4 million amputations and 0.125 million deaths - are recorded annually. The venom of saw-scaled and carpet vipers accounts for most cases of human death by snake bite in northern Africa and Asia. Although available antivenom therapy can prevent death, it fails to inhibit viper bite-induced tissue destruction. Specifically, it is known that the venom of the saw-scaled viper Echis carinatus attracts white blood cells called neutrophils to the bite site; however, the precise role of these cells in tissue destruction has been unclear up to now.
Kempaiah Kemparaju and colleagues inject E. carinatus venom into the tails of mice (in groups of about ten across several experiments) and show that the venom causes neutrophil self-destruction by inducing formation of neutrophil extracellular traps (NETs) - antimicrobial agents made of specific proteins and genetic material. When venom injection takes place, NETs capture the venom in order to prevent its rapid distribution through the body, but they also block blood vessels in the vicinity of the injection site, promoting tissue destruction. The authors demonstrate that NETs can be degraded by externally added DNase1, an enzyme that degrades DNA, which is a major component of NETs. Mice injected with DNAse1 and with the venom do not develop NETs, and are not affected by venom accumulation and tissue destruction at the injected site, but have greater mortality rates due to increased venom spread. However, the authors find that when DNase1 was injected 30 or 180 minutes after venom injection tissue destruction was prevented and this was not accompanied by an increase in mortality.
These results, if shown to be valid in humans, suggest that specifically-timed treatment with DNase1 may have a therapeutic potential for preventing tissue destruction caused by snake venom.
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