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Alleviation of viper venom induced platelet apoptosis by crocin (Crocus sativus): implications for thrombocytopenia in viper bites

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Abstract

Viper envenomations are characterized by prominent local and systemic manifestations including hematological alterations. Snake venom metalloproteinases (SVMPs) and phospholipase A2 (PLA2) plays crucial role in the pathophysiology of hemorrhage by targeting/altering the platelets function which may result in thrombocytopenia. Platelets undergo the classic events of mitochondria-mediated apoptotic pathway due to augmented endogenous reactive oxygen species (ROS) levels. The observed anticoagulant effects during viper envenomations could be due to exacerbated platelet apoptosis and thrombocytopenia. Moreover, antivenin treatments are ineffective against the venom-induced oxidative stress; therefore, it necessitates an auxiliary therapy involving antioxidants which can effectively scavenge the endothelium-generated/endogenous ROS and protect the platelets. The present study explored the effects of viper venom on platelet apoptosis and its amelioration by a phytochemical crocin. The study evaluated the Vipera russelli venom-induced apoptotic events including endogenous ROS generation, intracellular Ca2+ mobilization, mitochondrial membrane depolarization, cyt-c translocation, caspase activation and phosphatidylserine externalization which were effectively mitigated when the venom was pre-treated with crocin. The study highlights one of the less studied features of venom-induced secondary complications i.e. platelet apoptosis and sheds light on the underlying basis for venom-induced thrombocytopenia, systemic hemorrhage and in vivo anticoagulant effect.

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Acknowledgments

Sebastin Santhosh. M thank the Council of Scientific and Industrial Research (CSIR), Government of India, New Delhi, India, for financial assistance (SRF- Ref: 9/119(0191)2K12EMR-I dated 28-02-2012. Authors thank central instrumentation facility, University of Mysore, Institute of Excellence Project, MHRD (Government of India).

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore, 570 006, Karnataka, India

    M. Sebastin Santhosh, R. M. Thushara, M. Hemshekhar, K. Sunitha, K. Kemparaju & K. S. Girish

  2. Department of PG Studies and Research in Biochemistry, Tumkur University, Tumkur, 572103, Karnataka, India

    S. Devaraja

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  1. M. Sebastin Santhosh
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  2. R. M. Thushara
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  3. M. Hemshekhar
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  4. K. Sunitha
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Correspondence to K. S. Girish.

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Santhosh, M.S., Thushara, R.M., Hemshekhar, M. et al. Alleviation of viper venom induced platelet apoptosis by crocin (Crocus sativus): implications for thrombocytopenia in viper bites. J Thromb Thrombolysis 36, 424–432 (2013). https://doi.org/10.1007/s11239-013-0888-x

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