Oxidative stress and antioxidant defense in detoxification systems of snake venom-induced toxicity

 

Degang Dong1,2, Zhongping Deng2, Zhangren Yan3, Wenli Mao3, Jun Yi3, Mei Song4,5, Qiang Li3, Jun Chen3, Qi Chen3, Liang Liu3, Xi Wang3, Xiuqin Huang3, Wanchun Wang3

 

1 School of Life Sciences, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

2 Innovative Chinese Medicine Research Institute, Shanghai University of Chinese Medicine, Shanghai, China.

3 Southern Snake Bite Control Center, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

4 Science and Technology College, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

5 College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China

 

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.

 

Keywords: Snake Venom Proteome Hydrogen peroxide Antioxidant defense

 

Correspondence: 1210569577@qq.com

 

Received: 16 April 2020; Accepted: 08 September 2020; Published online: 19 October 2020.