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A Biochemical and Pharmacological Characterization of Phospholipase A2 and Metalloproteinase Fractions from Eastern Russell’s Viper (Daboia siamensis) Venom: Two Major Components Associated with Acute Kidney Injury

1
Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand
2
Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, Thailand
3
Institute of Pathology, Ministry of Public Health, Bangkok 10400, Thailand
4
Kulliyyah of Pharmacy, International Islamic University Malaysia, Bandar Indera Mahkota, Kuantan 25200, Malaysia
5
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 46150, Malaysia
6
Department of Pathology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand
7
Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia
*
Author to whom correspondence should be addressed.
Toxins 2021, 13(8), 521; https://doi.org/10.3390/toxins13080521
Received: 30 June 2021 / Revised: 19 July 2021 / Accepted: 21 July 2021 / Published: 26 July 2021
(This article belongs to the Special Issue Venom-Induced Tissue Damage)
Acute kidney injury (AKI) following Eastern Russell’s viper (Daboia siamensis) envenoming is a significant symptom in systemically envenomed victims. A number of venom components have been identified as causing the nephrotoxicity which leads to AKI. However, the precise mechanism of nephrotoxicity caused by these toxins is still unclear. In the present study, we purified two proteins from D. siamensis venom, namely RvPLA2 and RvMP. Protein identification using LCMS/MS confirmed the identity of RvPLA2 to be snake venom phospholipase A2 (SVPLA2) from Thai D. siamensis venom, whereas RvMP exhibited the presence of a factor X activator with two subunits. In vitro and in vivo pharmacological studies demonstrated myotoxicity and histopathological changes of kidney, heart, and spleen. RvPLA2 (3–10 µg/mL) caused inhibition of direct twitches of the chick biventer cervicis muscle preparation. After administration of RvPLA2 or RvMP (300 µg/kg, i.p.) for 24 h, diffuse glomerular congestion and tubular injury with minor loss of brush border were detected in envenomed mice. RvPLA2 and RvMP (300 µg/kg; i.p.) also induced congestion and tissue inflammation of heart muscle as well as diffuse congestion of mouse spleen. This study showed the significant roles of PLA2 and SVMP in snake bite envenoming caused by Thai D. siamensis and their similarities with observed clinical manifestations in envenomed victims. This study also indicated that there is a need to reevaluate the current treatment strategies for Thai D. siamensis envenoming, given the potential for irreversible nephrotoxicity. View Full-Text
Keywords: phospholipase A2; venom; nephrotoxicity; Russell’s viper; myotoxicity; kidney phospholipase A2; venom; nephrotoxicity; Russell’s viper; myotoxicity; kidney
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MDPI and ACS Style

Chaisakul, J.; Khow, O.; Wiwatwarayos, K.; Rusmili, M.R.A.; Prasert, W.; Othman, I.; Abidin, S.A.Z.; Charoenpitakchai, M.; Hodgson, W.C.; Chanhome, L.; Chaiyabutr, N. A Biochemical and Pharmacological Characterization of Phospholipase A2 and Metalloproteinase Fractions from Eastern Russell’s Viper (Daboia siamensis) Venom: Two Major Components Associated with Acute Kidney Injury. Toxins 2021, 13, 521. https://doi.org/10.3390/toxins13080521

AMA Style

Chaisakul J, Khow O, Wiwatwarayos K, Rusmili MRA, Prasert W, Othman I, Abidin SAZ, Charoenpitakchai M, Hodgson WC, Chanhome L, Chaiyabutr N. A Biochemical and Pharmacological Characterization of Phospholipase A2 and Metalloproteinase Fractions from Eastern Russell’s Viper (Daboia siamensis) Venom: Two Major Components Associated with Acute Kidney Injury. Toxins. 2021; 13(8):521. https://doi.org/10.3390/toxins13080521

Chicago/Turabian Style

Chaisakul, Janeyuth, Orawan Khow, Kulachet Wiwatwarayos, Muhamad R.A. Rusmili, Watcharamon Prasert, Iekhsan Othman, Syafiq A.Z. Abidin, Mongkon Charoenpitakchai, Wayne C. Hodgson, Lawan Chanhome, and Narongsak Chaiyabutr. 2021. "A Biochemical and Pharmacological Characterization of Phospholipase A2 and Metalloproteinase Fractions from Eastern Russell’s Viper (Daboia siamensis) Venom: Two Major Components Associated with Acute Kidney Injury" Toxins 13, no. 8: 521. https://doi.org/10.3390/toxins13080521

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