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Published on: July 7, 2014
Oxidative stress and antioxidant defense in detoxification systems of snake venom-induced toxicity
Degang Dong1,2, Zhongping Deng2, Zhangren Yan3
1School of Life Sciences, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
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.
Insights
Snakebite toxicity pathways involve a protein network regulating oxidative stress. This network interacts with hydrogen peroxide, offering insights into venom-induced toxicity mechanisms and potential treatments.
Area of Science:
- Biochemistry
- Toxicology
- Proteomics
Background:
- Snakebites are a global health threat with diagnostic challenges.
- Understanding venom toxicity pathways is crucial for effective treatment.
- Traditional Chinese Medicine categorizes snakebites as wind, fire, or wind-fire toxins.
Purpose of the Study:
- To identify diagnostic biomarkers for snake venom toxicity.
- To elucidate the protein expression profiles and pathways involved in snake venom toxicity.
- To investigate the differences between fire and wind-fire toxin-induced snakebites.
Main Methods:
- Serum protein quantification using LC-MS/MS in snakebite patients.
- Identification of differentially abundant proteins (DAPs) compared to healthy controls.
- Construction of protein-protein interaction networks using the STITCH database.
Main Results:
- Distinct protein expression profiles were observed between wind-fire and fire toxins.
- 93 DAPs were identified in each subgroup, with 38 showing significant expression differences.
- DAPs were involved in oxygen transport, hydrogen peroxide catabolism, and heme binding, forming a network centered on hydrogen peroxide.
Conclusions:
- Snake venom toxicity pathways involve a protein network regulating oxidative stress.
- This network interacts with hydrogen peroxide, suggesting a role in antioxidant defense.
- Findings provide insights into venom-induced toxicity mechanisms and potential therapeutic targets.
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