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

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