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Progressive Hemorrhage and Myotoxicity Induced by Echis carinatus Venom in Murine Model: Neutralization by Inhibitor Cocktail of N,N,N',N'-Tetrakis (2-Pyridylmethyl) Ethane-1,2-Diamine and Silymarin

Viperbite is often associated with severe local toxicity, including progressive hemorrhage and myotoxicity, persistent even after the administration of anti-snake venom (ASV). In the recent past, investigations have revealed the orchestrated actions of Zn(2+) metalloproteases (Zn(2+)MPs), phospholip...

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Autores principales: Nanjaraj Urs, Ankanahalli N., Ramakrishnan, Chandrasekaran, Joshi, Vikram, Suvilesh, Kanve Nagaraj, Veerabasappa Gowda, Teregowda, Velmurugan, Devadasan, Vishwanath, Bannikuppe Sannanaik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537139/
https://www.ncbi.nlm.nih.gov/pubmed/26274501
http://dx.doi.org/10.1371/journal.pone.0135843
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author Nanjaraj Urs, Ankanahalli N.
Ramakrishnan, Chandrasekaran
Joshi, Vikram
Suvilesh, Kanve Nagaraj
Veerabasappa Gowda, Teregowda
Velmurugan, Devadasan
Vishwanath, Bannikuppe Sannanaik
author_facet Nanjaraj Urs, Ankanahalli N.
Ramakrishnan, Chandrasekaran
Joshi, Vikram
Suvilesh, Kanve Nagaraj
Veerabasappa Gowda, Teregowda
Velmurugan, Devadasan
Vishwanath, Bannikuppe Sannanaik
author_sort Nanjaraj Urs, Ankanahalli N.
collection PubMed
description Viperbite is often associated with severe local toxicity, including progressive hemorrhage and myotoxicity, persistent even after the administration of anti-snake venom (ASV). In the recent past, investigations have revealed the orchestrated actions of Zn(2+) metalloproteases (Zn(2+)MPs), phospholipase A(2)s (PLA(2)s) and hyaluronidases (HYs) in the onset and progression of local toxicity from the bitten site. As a consequence, venom researchers and medical practitioners are in deliberate quest of potent molecules alongside ASV to tackle the brutal local manifestations induced by aforesaid venom toxins. Based on these facts, we have demonstrated the protective efficacy of inhibitor cocktail containing equal ratios of N,N,N’,N’-tetrakis (2-pyridylmethyl) ethane-1,2-diamine (TPEN) and silymarin (SLN) against progressive local toxicity induced by Echis carinatus venom (ECV). In our previous study we have shown the inhibitory potentials of TPEN towards Zn(2+)MPs of ECV (IC(50): 6.7 μM). In this study we have evaluated in vitro inhibitory potentials of SLN towards PLA(2)s (IC(50:) 12.5 μM) and HYs (IC(50:) 8 μM) of ECV in addition to docking studies. Further, we have demonstrated the protection of ECV induced local toxicity with 10 mM inhibitor cocktail following 15, 30 min (for hemorrhage and myotoxicity); 60 min (for hemorrhage alone) of ECV injection in murine model. The histological examination of skin and thigh muscle sections taken out from the site of ECV injection substantiated the overall protection offered by inhibitor cocktail. In conclusion, the protective efficacy of inhibitor cocktail is of high interest and can be administered locally alongside ASV to treat severe local toxicity.
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spelling pubmed-45371392015-08-20 Progressive Hemorrhage and Myotoxicity Induced by Echis carinatus Venom in Murine Model: Neutralization by Inhibitor Cocktail of N,N,N',N'-Tetrakis (2-Pyridylmethyl) Ethane-1,2-Diamine and Silymarin Nanjaraj Urs, Ankanahalli N. Ramakrishnan, Chandrasekaran Joshi, Vikram Suvilesh, Kanve Nagaraj Veerabasappa Gowda, Teregowda Velmurugan, Devadasan Vishwanath, Bannikuppe Sannanaik PLoS One Research Article Viperbite is often associated with severe local toxicity, including progressive hemorrhage and myotoxicity, persistent even after the administration of anti-snake venom (ASV). In the recent past, investigations have revealed the orchestrated actions of Zn(2+) metalloproteases (Zn(2+)MPs), phospholipase A(2)s (PLA(2)s) and hyaluronidases (HYs) in the onset and progression of local toxicity from the bitten site. As a consequence, venom researchers and medical practitioners are in deliberate quest of potent molecules alongside ASV to tackle the brutal local manifestations induced by aforesaid venom toxins. Based on these facts, we have demonstrated the protective efficacy of inhibitor cocktail containing equal ratios of N,N,N’,N’-tetrakis (2-pyridylmethyl) ethane-1,2-diamine (TPEN) and silymarin (SLN) against progressive local toxicity induced by Echis carinatus venom (ECV). In our previous study we have shown the inhibitory potentials of TPEN towards Zn(2+)MPs of ECV (IC(50): 6.7 μM). In this study we have evaluated in vitro inhibitory potentials of SLN towards PLA(2)s (IC(50:) 12.5 μM) and HYs (IC(50:) 8 μM) of ECV in addition to docking studies. Further, we have demonstrated the protection of ECV induced local toxicity with 10 mM inhibitor cocktail following 15, 30 min (for hemorrhage and myotoxicity); 60 min (for hemorrhage alone) of ECV injection in murine model. The histological examination of skin and thigh muscle sections taken out from the site of ECV injection substantiated the overall protection offered by inhibitor cocktail. In conclusion, the protective efficacy of inhibitor cocktail is of high interest and can be administered locally alongside ASV to treat severe local toxicity. Public Library of Science 2015-08-14 /pmc/articles/PMC4537139/ /pubmed/26274501 http://dx.doi.org/10.1371/journal.pone.0135843 Text en © 2015 Nanjaraj Urs et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Nanjaraj Urs, Ankanahalli N.
Ramakrishnan, Chandrasekaran
Joshi, Vikram
Suvilesh, Kanve Nagaraj
Veerabasappa Gowda, Teregowda
Velmurugan, Devadasan
Vishwanath, Bannikuppe Sannanaik
Progressive Hemorrhage and Myotoxicity Induced by Echis carinatus Venom in Murine Model: Neutralization by Inhibitor Cocktail of N,N,N',N'-Tetrakis (2-Pyridylmethyl) Ethane-1,2-Diamine and Silymarin
title Progressive Hemorrhage and Myotoxicity Induced by Echis carinatus Venom in Murine Model: Neutralization by Inhibitor Cocktail of N,N,N',N'-Tetrakis (2-Pyridylmethyl) Ethane-1,2-Diamine and Silymarin
title_full Progressive Hemorrhage and Myotoxicity Induced by Echis carinatus Venom in Murine Model: Neutralization by Inhibitor Cocktail of N,N,N',N'-Tetrakis (2-Pyridylmethyl) Ethane-1,2-Diamine and Silymarin
title_fullStr Progressive Hemorrhage and Myotoxicity Induced by Echis carinatus Venom in Murine Model: Neutralization by Inhibitor Cocktail of N,N,N',N'-Tetrakis (2-Pyridylmethyl) Ethane-1,2-Diamine and Silymarin
title_full_unstemmed Progressive Hemorrhage and Myotoxicity Induced by Echis carinatus Venom in Murine Model: Neutralization by Inhibitor Cocktail of N,N,N',N'-Tetrakis (2-Pyridylmethyl) Ethane-1,2-Diamine and Silymarin
title_short Progressive Hemorrhage and Myotoxicity Induced by Echis carinatus Venom in Murine Model: Neutralization by Inhibitor Cocktail of N,N,N',N'-Tetrakis (2-Pyridylmethyl) Ethane-1,2-Diamine and Silymarin
title_sort progressive hemorrhage and myotoxicity induced by echis carinatus venom in murine model: neutralization by inhibitor cocktail of n,n,n',n'-tetrakis (2-pyridylmethyl) ethane-1,2-diamine and silymarin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537139/
https://www.ncbi.nlm.nih.gov/pubmed/26274501
http://dx.doi.org/10.1371/journal.pone.0135843
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