Abstract

Increasing evidence suggests a sizable involvement of hemotoxins in the morbidity associated with envenomation by the Indian spectacled cobra, Naja naja (N.N). This study investigates the ability of Indian polyvalent anti-snake venom (ASV), methanolic extract of Andrographis paniculata (MAP) and their combination in reversing the hemostatic abnormalities, viz. activated partial thromboplastin time(aPTT), prothrombin time(PT) and thrombin time(TT) in citrated plasma. These parameters were assessed in 2 groups of experiments. Group 1: Without the prior incubation of plasma with venom and Group 2: With prior incubation of plasma with venom for 90 min at 37°C. Venom caused significant (p < 0.001) prolongation in aPTT (175%), PT (49%) and TT (34%) in Group 1 and ASV could completely bring them back to normal. MAP showed a concentration-dependent reversal in aPTT, normalization of PT and prolongation of TT. When low concentration of ASV was supplemented with MAP, their combined effect in normalizing aPTT and PT improved by 37% and 26% respectively when compared to ASV alone. In Group 2, venom caused significant (p < 0.001) prolongation in aPTT (231%), PT (312%) and TT (245%). ASV had limited effect in reversing aPTT (52%), TT (31%) but completely normalized PT. MAP was marginally effective in reversing the prolonged aPTT and PT but caused further prolongation of TT. Combination of ASV and MAP was more effective than ASV alone in reversing venom-induced increase in aPTT (52%) and PT (29%). The study proved that, a drastic reduction of ASV by 70%, could be effectively supplemented by MAP in combating hemostatic abnormalities induced by NN venom.

Highlights

  • The venom of the Indian spectacled cobra, Naja naja (N.N) is a cocktail of 81 different toxins (Choudhury et al, 2017)

  • Further increase in methanolic extract of Andrographis paniculata (MAP) concentration up to 180 μg caused a prolongation of activated partial thromboplastin time (aPTT)

  • This study was an evaluation of the ability of anti-snake venom (ASV), MAP and their combination to normalize the hemostatic abnormalities induced by Naja naja (NN) venom

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Summary

Introduction

The venom of the Indian spectacled cobra, Naja naja (N.N) is a cocktail of 81 different toxins (Choudhury et al, 2017). Increasing evidence suggests a sizable involvement of hemotoxins in the morbidity associated with N.N bite, causing wide-spread changes in hemostasis These effects are mediated by toxins that affect platelet aggregation (Kumar et al, 2010), coagulation (Berling and Isbister, 2015), hemolysis (Dissanayake et al, 2018) and fibrinogenolysis (Gowda et al, 2006; Kumar et al, 2010). NN-PF3, a metalloprotease from N.N venom with molecular mass 67.81 KDa, prolonged aPTT, PT, TT, exhibited fibrin(ogen)olytic activity which was inhibited by polyvalent anti-snake venom (ASV). It did not affect the activity of thrombin. These changes were completely reversed by ASV and the methanolic extract of Andrographis paniculata (MAP) when used individually or in combination (Nayak, Ahammad, et al, 2020)

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