Lupeol derivative mitigates echis carinatus venom-induced tissue destruction by neutralizing venom toxins and protecting collagen and angiogenic receptors on inflammatory cells

Katkar, G. D. and Sharma, R. D. and Vishalakshi, G. J. and Naveenkumar, S. K. and Madhur, G. and Thushara, R. M. and Narender, T. and Girish, K. S. and Kemparaju, K. (2015) Lupeol derivative mitigates echis carinatus venom-induced tissue destruction by neutralizing venom toxins and protecting collagen and angiogenic receptors on inflammatory cells. Biochimica Et Biophysica Acta-General Subjects, 1850 (12). pp. 2393-2409. ISSN 0304-4165

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Official URL: http:://doi.org/10.1016/j.bbagen.2015.09.011

Abstract

Background: Echis carinatus bite is a serious threat in South-Asian countries including India, as it causes highest number of deaths and terrifying long-term tissue destruction at the bitten site. Although venom metalloproteinases and hyaluronidases are the suggested key players, studies on the effect of venom on polymorphonuclear cells, peripheral blood mononuclear cells and platelets, and their role in long-term tissue destruction are still in infancy. While, the effect of venom on collagen receptors, integrin alpha 2 beta 1/GP VI/DDR1 and CX3CR1 chemokine receptor present on these cells is an untouched area. Methods: Lupeol, lupeol acetate, its synthetic derivatives 2-8 were screened for inhibition of E. carinatus venom induced-hemorrhage in mouse model where compound 8 was found to be the most potent. Further, compounds efficiently neutralized venom induced hemorrhage, edema, dermonecrosis, myonecrosis, myotoxicity, procoagulant, oxidative stress, inflammatory cytokines and cleavage of collagen and CX3CR1 receptors on inflammatory cells in in vivo, in silico, ex vivo and in vitro studies. Conclusions: This study for the first time demonstrated the cleavage of collagen receptors and the receptor for angiogenesis and wound healing by the venom and its inhibition by compound 8, as these are important for firm adhesion of inflammatory cells at the damaged site to resolve inflammation and promote tissue repair. General significance: This study provides a lead in venom pharmacology, wherein, compound 8 could be a therapeutic agent for the better management of viper venom-induced long-term tissue destruction. (C) 2015 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: E. carinatus; Venom; Local toxicity; Lupeol; Collagen receptors; Inflammatory cells
Subjects: C Chemical Science > Biochemistry
Divisions: Department of > Biochemistry
Depositing User: Shrirekha N
Date Deposited: 29 May 2019 07:10
Last Modified: 17 Sep 2019 10:04
URI: http://eprints.uni-mysore.ac.in/id/eprint/618

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