TY - JOUR
T1 - A biochemical and pharmacological characterization of phospholipase a2 and metalloproteinase fractions from eastern russell’s viper (Daboia siamensis) venom
T2 - Two major components associated with acute kidney injury
AU - Chaisakul, Janeyuth
AU - Khow, Orawan
AU - Wiwatwarayos, Kulachet
AU - Rusmili, Muhamad Rusdi Ahmad
AU - Prasert, Watcharamon
AU - Othman, Iekhsan
AU - Abidin, Syafiq Asnawi Zainal
AU - Charoenpitakchai, Mongkon
AU - Hodgson, Wayne C.
AU - Chanhome, Lawan
AU - Chaiyabutr, Narongsak
N1 - Funding Information:
Funding: This research was funded by Research Grant from Phramongkutklao College of Medicine, Bangkok, Thailand. M.R.A.R. was supported by the Research Incentive Grant Scheme of International Islamic University Malaysia (grant no. RIGS 17-007-0582). W.C.H. was supported by an Australian National Health and Medical Research Council (NHMRC) Centres for Research Excellence Grant (ID:1110343).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - Kidney
KW - Myotoxicity
KW - Nephrotoxicity
KW - Phospholipase A
KW - Russell’s viper
KW - Venom
UR - http://www.scopus.com/inward/record.url?scp=85111712365&partnerID=8YFLogxK
U2 - 10.3390/toxins13080521
DO - 10.3390/toxins13080521
M3 - Article
C2 - 34437392
AN - SCOPUS:85111712365
VL - 13
JO - Toxins
JF - Toxins
SN - 2072-6651
IS - 8
M1 - 521
ER -