Victims of
Bothrops jararaca snakebites manifest bleedings,
blood incoagulability,
platelet dysfunction, and
thrombocytopenia, and the latter has been directly implicated in the genesis of
hemorrhagic diathesis. We addressed herein the direct effects of B.
jararaca venom (BjV) on ex vivo
platelet aggregation and granule
secretion in washed
human and
mouse platelets. BjV directly aggregated
platelets, but the extent of
platelet aggregation was lower in
human than
mouse platelets. On the other
hand, BjV (24.4 mu g/mL) and
thrombin (0.1 U/mL) induced a
similar extent of
ATP and
platelet factor 4 (PF4)
secretion in both species. BjV-induced
platelet aggregation was independent of the
platelet dense body content, as in pearl
mouse (Ap3b1(-/-))
platelets, whose dense bodies are deficient in
adenine nucleotides and
serotonin, the extent of
platelet aggregation was superior to that induced in BALB/c or C57BL/6
mice. BjV-induced
beta-hexosaminidase secretion in
human platelets was less intense than that evoked by
thrombin, and the contrary was observed in
mouse platelets. Irreversible inactivation of
platelet cyclooxygenase 1 by
acetylsalicylic acid did not reduce BjV-induced
platelet aggregation. BjV exerted no cytotoxic activity in
human and
mouse platelets, as evaluated by
lactate dehydrogenase loss.
Eptifibatide, which inhibits the binding of
fibrinogen to
platelet glycoprotein complex GPIIb-IIIa, differently blocked BjV-induced
platelet aggregation in
mice and
humans. BjV-induced
platelet aggregation did not depend on
snake venom serine proteinases nor
metalloproteinases in
mice, whilst
serine proteinases were rather important for
platelet aggregation in
humans. Our results show that BjV induces direct activation, aggregation, and
secretion in
human and
mouse platelets, but it exerts diverse responses in them, which should be considered in
comparative studies to understand pathophysiological events during
Bothrops envenomation.