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

Janeyuth Chaisakul, Orawan Khow, Kulachet Wiwatwarayos, Muhamad Rusdi Ahmad Rusmili, Watcharamon Prasert, Iekhsan Othman, Syafiq Asnawi Zainal Abidin, Mongkon Charoenpitakchai, Wayne C. Hodgson, Lawan Chanhome, Narongsak Chaiyabutr

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Abstract

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 con-firmed 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.

Original languageEnglish
Article number521
Number of pages18
JournalToxins
Volume13
Issue number8
DOIs
Publication statusPublished - Aug 2021

Keywords

  • Kidney
  • Myotoxicity
  • Nephrotoxicity
  • Phospholipase A
  • Russell’s viper
  • Venom

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