Abstract
Background: Snakebites remain a major life-threatening event worldwide. It is still difficult to make a positive identification of snake species by clinicians in both Western medicine and Chinese medicine. The main reason for this is a shortage of diagnostic biomarkers and lack of knowledge about pathways of venom-induced toxicity. In traditional Chinese medicine, snakebites are considered to be treated with wind, fire, and wind-fire toxin, but additional studies are required.Methods: Cases of snakebite seen at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were grouped as follows: fire toxin - including four cases of bites by Agkistrodon acutus and three bites by Trimeresurus stejnegeri - and wind-fire toxin - four cases of bites by vipers and three bites by cobras. Serum protein quantification was performed using LC-MS/MS. Differential abundance proteins (DAPs) were identified from comparison of snakebites of each snake species and healthy controls. The protein interaction network was constructed using STITCH database. Results: Principal component analysis and hierarchical clustering of 474 unique proteins exhibited protein expression profiles of wind-fire toxins that are distinct from that of fire toxins. Ninety-three DAPs were identified in each snakebite subgroup as compared with healthy control, of which 38 proteins were found to have significantly different expression levels and 55 proteins displayed no expression in one subgroup, by subgroup comparison. GO analysis revealed that the DAPs participated in bicarbonate/oxygen transport and hydrogen peroxide catabolic process, and affected carbon-oxygen lyase activity and heme binding. Thirty DAPs directly or indirectly acted on hydrogen peroxide in the interaction network of proteins and drug compounds. The network was clustered into four groups: lipid metabolism and transport; IGF-mediated growth; oxygen transport; and innate immunity.Conclusions: Our results show that the pathways of snake venom-induced toxicity may form a protein network of antioxidant defense by regulating oxidative stress through interaction with hydrogen peroxide.
Highlights
Snakebites remain a major life-threatening event worldwide
Ninety-three differential abundance proteins (DAPs) were identified in each snakebite subgroup as compared with healthy control, of which 38 proteins were found to have significantly different expression levels and 55 proteins displayed no expression in one subgroup, by subgroup comparison
Gene Ontology (GO) analysis revealed that the DAPs participated in bicarbonate/ oxygen transport and hydrogen peroxide catabolic process, and affected carbon-oxygen lyase activity and heme binding
Summary
It is still difficult to make a positive identification of snake species by clinicians in both Western medicine and Chinese medicine. Venomous snakebites have been a common and critical clinical illness since ancient times [1]. The popular story about the farmer and the snake from Aesop’s Fables illustrates that fatal snake bites were one of the major public health challenges. The World Health Organization estimated that about 4.5 to 5.4 million snake bites occur globally each year, resulting in 1.8 to 2.7 million cases of snakebite envenomings and 81,000 to 138,000 deaths [2]. Bites by dangerous snakes are greatly feared, and effective symptomatic diagnosis and treatment are poorly documented. Due to complex pathogenesis and interspecific variability of venom components, the mechanisms and pathophysiological changes are still not completely elucidated [8, 9]
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