Oxidative stress-induced methemoglobinemia is the silent killer during snakebite: a novel and strategic neutralization by melatonin

Sharma, R. D. and Katkar, G. D. and Sundaram, M. S. and Paul, M. and NaveenKumar, S. K. and Swethakumar, B. and Hemshekhar, M. and Girish, K. S. and Kemparaju, K. (2015) Oxidative stress-induced methemoglobinemia is the silent killer during snakebite: a novel and strategic neutralization by melatonin. JOURNAL OF PINEAL RESEARCH, 59 (2). pp. 240-254. ISSN 1600-079X

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Official URL: http://doi.org/10.1111/jpi.12256

Abstract

Oxidative stress-induced methemoglobinemia remained an untouched area in venom pharmacology till date. This study for the first time explored the potential of animal venoms to oxidize hemoglobin to methemoglobin. In invitro whole-blood assay, methemoglobin forming ability of venoms varied as Naja naja>Ophiophagus hannah>Echis carinatus>Daboia russellii>Apis mellifera>Mesobuthus tamulus>Hippasa partita. Being highly potential, N.naja venom was further studied to observe methemoglobin formation in RBCs and in combinations with PMNs and PBMCs, where maximum effect was observed in RBCs+PMNs combination. Naja naja venom/externally added methemoglobin-induced methemoglobin formation was in parallel with ROS generation in whole blood/RBCs/RBCs+PMNs/RBCs+PBMCs. In invivo studies, the lethal dose (1mg/kg body weight, i.p.) of N.naja venom readily induced methemoglobin formation, ROS generation, expression of inflammatory markers, and hypoxia-inducible factor-3. Although the mice administered with three effective doses of antivenom recorded zero mortality; the methemoglobin and ROS levels remained high. However, one effective dose of antivenom when administered along with melatonin (1:50; venom/melatonin, w/w), not only offered 100% survival of experimental mice, but also significantly reduced methemoglobin level, and oxidative stress markers including hypoxia-inducible factor-3. This study provides strong drive that, complementing melatonin would not only reduce the antivenom load, but for sure greatly increase the success rate of antivenom therapy and drastically minimize the global incidence of snakebite deaths. However, further detailed investigations are needed before translating the combined therapy towards the bed side.

Item Type: Article
Uncontrolled Keywords: antivenom; hypoxia; melatonin; methemoglobin; oxidative stress; red blood cells; venom
Subjects: C Chemical Science > Biochemistry
Divisions: Department of > Biochemistry
Depositing User: Shrirekha N
Date Deposited: 31 May 2019 07:22
Last Modified: 31 May 2019 07:22
URI: http://eprints.uni-mysore.ac.in/id/eprint/746

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