Pharmacological and biochemical studies on the venom of a clinically important viper snake (Echis carinatus) of Pakistan Q3 Arifa Savanur a, b , Syed Abid Ali b, * , Iqra Munir b , Atiya Abbasi b , Mehtab Alam b , Hilal Ahmed Shaikh a a Neuromuscular Research Unit, Department of Physiology, University of Karachi, Karachi 75270, Pakistan b H.E.J Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan article info Article history: Received 9 September 2013 Received in revised form 7 January 2014 Accepted 9 January 2014 Available online xxxx Keywords: Echis carinatus venom Rabbit ileum Active tension Potassium chloride Acetylcholine Contracture abstract Echis carinatus (saw-scaled viper) has been the major culprit responsible for serious en- venomation casualties throughout the subcontinent. The present study describes the electrophoretic and zymographic characterization of E. carinatus venom and its effect on mammalian smooth muscle. Crude venom showed the presence of disintegrin, PLA 2 , C- type lectin/lectin-like components, CRISP, Serine protease, L-amino acid oxidase and very high concentrations of SVMPs. E. carinatus venom (1, 10, 30, 50, 100 mg/ml) inhibited the active tension/force of muscle contraction in a time and concentration dependent manner. The observed effects abolished when the venom was heated at 100  C for 5 min. However, a decrease in bath temperature from 37  C to 26  C or an increase in CaCl 2 concentration to 5 mM did not prevent the inhibition of contractile activity. The contractile response eli- cited by exogenous application of 50 mM KCl and 1 mM acetylcholine (ACh) was also significantly inhibited by all venom concentrations. Prior administration of commercially available polyvalent anti-venom partially neutralized and prevented the effect of E. car- inatus venom whereas addition of anti-venom at t 50 failed to reverse the inhibitory effect. Studies on isolated intestinal muscle indicate involvement of myotoxic and apoptotic components in E. carinatus venom for irreversible damage to muscle tissue. Ó 2014 Elsevier Ltd. All rights reserved. 1. Introduction Snake bites are common throughout the world and according to WHO statistics more than 5.5 million people are bitten by snakes each year (Kasturiratne et al., 2008). Of these bites from venomous snakes claim 94,000– 1,25,000 lives while others suffer amputations, infections, tetanus, scarring, contractures, psychological sequelae etc. (http://www.who.int/mediacentre/factsheets/fs373/ en/). However the burden is greater in African and Asian countries like Bangladesh (6000 deaths/year), Cameroon, Ghana, India (50,000 deaths/year), Indonesia, Mali, Nigeria, Pakistan (20,000 deaths) etc. which lack quick treatment facilities i.e. availability of specific anti- venom (Warrell, 2010, 1995; Kochar et al., 2007; Cruz et al., 2009; Mohapatra et al., 2011; Whitaker and Whitaker, 2012). Among the several hundred venomous snakes, vipers belonging to the genus Echis are clinically the most important (WHO category 1, http://apps.who. int/bloodproducts/snakeantivenoms/database/; Casewell et al., 2010). These snakes are native of Northern Africa, Middle East, Central Asia, Afghanistan, Bangladesh, India, Nepal, Pakistan, Sri Lanka etc. where they cause more * Corresponding author. Tel.: þ92 021 111 222 292x120/127, þ92 333 3456872; fax: þ92 21 34819018 19. E-mail addresses: dr.syedabidali@gmail.com, abid.ali@iccs.edu (S.A. Ali). Contents lists available at ScienceDirect Toxicon journal homepage: www.elsevier.com/locate/toxicon 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 0041-0101/$ – see front matter Ó 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.toxicon.2014.01.005 Toxicon xxx (2014) 1–11 TOXCON4763_proof ■ 24 January 2014 ■ 1/11 Please cite this article in press as: Savanur, A., et al., Pharmacological and biochemical studies on the venom of a clinically important viper snake (Echis carinatus) of Pakistan, Toxicon (2014), http://dx.doi.org/10.1016/j.toxicon.2014.01.005