Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation
Abstract
:1. Introduction
2. Results
2.1. Inhibition of Phospholipase A2 In Vitro
- D. acutus, Y = 25.28X + 111.4, R2 = 0.9865; IC50 = 0.0037 μg/μL
- A. halys, AH: Y = 23.47X + 115.9, R2 = 0.9867; IC50 = 0.0016 μg/μL
- N. atra, Y = 22.36X + 76.82, R2 = 0.9916; IC50 = 0.063 μg/μL
- B. multicinctus, Y = 15.92X + 89.80, R2 = 0.9991. IC50 = 0.0032 μg/μL
2.2. Anti-Hemorrhage Effect In Vivo
2.3. Physiological and Behavioral Signs
2.4. Local Reaction in the Gastrocnemius Muscle
2.5. Immunohistochemistry and Desmin Loss
2.6. Biochemical Assays of Serum CK, LDH1, AST, and ALT Levels
2.7. The Estimation of the Median Effective Dose (ED50) of Varespladib
3. Discussion
4. Materials and Methods
4.1. Reagents and Materials
4.2. Inhibition of Varespladib on svPLA2 In Vitro
4.3. Anti-Hemorrhage Effect In Vivo
4.4. Inhibition to Myotoxicity
4.4.1. Desmin Degradation in Envenomed Gastrocnemius Muscle
4.4.2. Immunohistochemical Analysis
4.5. Estimation of the Median Effective Dose (ED50) of Varespladib against Snake Venoms
4.6. Statistical Analysis
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
CK | Creatine kinase |
LDH1 | Lactate dehydrogenase isoenzyme 1 |
AST | Aspartate transaminase |
ALT | Alanine transaminase |
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Sample Availability: Samples of the snake venom lyophilized powder of D. acutus, A. halys, B. multicinctus, and N. atra are available from the authors. |
Venom | Challenge Dose (μg) | ED50 (μg/g) (95% CI) | Standard Deviation |
---|---|---|---|
D. acutus | 240 | 1.14 (0.86–1.50) | 0.0608 |
A. halys | 120 | 0.45 (0.33–0.62) | 0.0699 |
B. multicinctus | 12 | 15.23 (12.08–19.23) | 0.0515 |
N. atra | 28 | 22.09(17.31–28.19) | 0.0540 |
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Wang, Y.; Zhang, J.; Zhang, D.; Xiao, H.; Xiong, S.; Huang, C. Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. Molecules 2018, 23, 391. https://doi.org/10.3390/molecules23020391
Wang Y, Zhang J, Zhang D, Xiao H, Xiong S, Huang C. Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. Molecules. 2018; 23(2):391. https://doi.org/10.3390/molecules23020391
Chicago/Turabian StyleWang, Yiding, Jing Zhang, Denghong Zhang, Huixiang Xiao, Shengwei Xiong, and Chunhong Huang. 2018. "Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation" Molecules 23, no. 2: 391. https://doi.org/10.3390/molecules23020391
APA StyleWang, Y., Zhang, J., Zhang, D., Xiao, H., Xiong, S., & Huang, C. (2018). Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. Molecules, 23(2), 391. https://doi.org/10.3390/molecules23020391