Efficacy of IgG and F(ab′)2 Antivenoms to Neutralize Snake Venom-induced Local Tissue Damage as Assessed by the Proteomic Analysis of Wound Exudate

Abstract

Proteomic analysis of wound exudates represents a valuable tool to investigate tissue pathology and to assess the therapeutic success of various interventions. In this study, the ability of horse-derived IgG and F(ab0)2 antivenoms to neutralize local pathological effects induced by the venom of the snake Bothrops asper in mouse muscle was investigated by the proteomic analysis of exudates collected in the vicinity of affected tissue. In experiments involving the incubation of venom and antivenom prior to injection in mice, hemorrhagic activity was completely abolished and local muscle damaging activity was significantly reduced by the antivenoms. In these conditions, the relative amounts of several intracellular and extracellular matrix proteins were reduced by the action of antivenoms, whereas the relative amounts of various plasma proteins were not modified. Because not all intracellular proteins were reduced, it is likely that there is a residual cytotoxicity not neutralized by antivenoms. In experiments designed to more closely reproduce the actual circumstances of envenoming, that is, when antivenom is administered after envenomation, the number of proteins whose amounts in exudates were reduced by antivenoms decreased, underscoring the difficulty in neutralizing local pathology due to the very rapid onset of venom-induced pathology. In these experiments, IgG antivenom was more efficient than F(ab0)2 antivenom when administered after envenomation, probably as a consequence of differences in their pharmacokinetic profiles.