A Biochemical and Pharmacological Characterization of Phospholipase A<sub>2</sub> and Metalloproteinase Fractions from Eastern Russell’s Viper (<i>Daboia siamensis</i>) Venom: Two Major Components Associated with Acute Kidney Injury
Acute kidney injury (AKI) following Eastern Russell’s viper (<i>Daboia siamensis</i>) 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...
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MDPI AG
2021-07-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Janeyuth Chaisakul |
| collection | DOAJ |
| description | Acute kidney injury (AKI) following Eastern Russell’s viper (<i>Daboia siamensis</i>) 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 <i>D. siamensis</i> venom, namely RvPLA<sub>2</sub> and RvMP. Protein identification using LCMS/MS confirmed the identity of RvPLA<sub>2</sub> to be snake venom phospholipase A<sub>2</sub> (SVPLA<sub>2</sub>) from Thai <i>D. siamensis</i> 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. RvPLA<sub>2</sub> (3–10 µg/mL) caused inhibition of direct twitches of the chick biventer cervicis muscle preparation. After administration of RvPLA<sub>2</sub> 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. RvPLA<sub>2</sub> 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 PLA<sub>2</sub> and SVMP in snake bite envenoming caused by Thai <i>D. siamensis</i> 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 <i>D. siamensis</i> envenoming, given the potential for irreversible nephrotoxicity. |
| first_indexed | 2024-03-10T08:19:11Z |
| format | Article |
| id | doaj.art-09d0f032ba434883b90d27f33e81fdea |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T08:19:11Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-09d0f032ba434883b90d27f33e81fdea2023-11-22T10:04:06ZengMDPI AGToxins2072-66512021-07-0113852110.3390/toxins13080521A Biochemical and Pharmacological Characterization of Phospholipase A<sub>2</sub> and Metalloproteinase Fractions from Eastern Russell’s Viper (<i>Daboia siamensis</i>) Venom: Two Major Components Associated with Acute Kidney InjuryJaneyuth Chaisakul0Orawan Khow1Kulachet Wiwatwarayos2Muhamad Rusdi Ahmad Rusmili3Watcharamon Prasert4Iekhsan Othman5Syafiq Asnawi Zainal Abidin6Mongkon Charoenpitakchai7Wayne C. Hodgson8Lawan Chanhome9Narongsak Chaiyabutr10Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok 10400, ThailandQueen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, ThailandInstitute of Pathology, Ministry of Public Health, Bangkok 10400, ThailandKulliyyah of Pharmacy, International Islamic University Malaysia, Bandar Indera Mahkota, Kuantan 25200, MalaysiaDepartment of Pharmacology, Phramongkutklao College of Medicine, Bangkok 10400, ThailandJeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 46150, MalaysiaJeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 46150, MalaysiaDepartment of Pathology, Phramongkutklao College of Medicine, Bangkok 10400, ThailandMonash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, AustraliaQueen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, ThailandQueen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, ThailandAcute kidney injury (AKI) following Eastern Russell’s viper (<i>Daboia siamensis</i>) 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 <i>D. siamensis</i> venom, namely RvPLA<sub>2</sub> and RvMP. Protein identification using LCMS/MS confirmed the identity of RvPLA<sub>2</sub> to be snake venom phospholipase A<sub>2</sub> (SVPLA<sub>2</sub>) from Thai <i>D. siamensis</i> 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. RvPLA<sub>2</sub> (3–10 µg/mL) caused inhibition of direct twitches of the chick biventer cervicis muscle preparation. After administration of RvPLA<sub>2</sub> 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. RvPLA<sub>2</sub> 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 PLA<sub>2</sub> and SVMP in snake bite envenoming caused by Thai <i>D. siamensis</i> 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 <i>D. siamensis</i> envenoming, given the potential for irreversible nephrotoxicity.https://www.mdpi.com/2072-6651/13/8/521phospholipase A<sub>2</sub>venomnephrotoxicityRussell’s vipermyotoxicitykidney |
| spellingShingle | 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 A Biochemical and Pharmacological Characterization of Phospholipase A<sub>2</sub> and Metalloproteinase Fractions from Eastern Russell’s Viper (<i>Daboia siamensis</i>) Venom: Two Major Components Associated with Acute Kidney Injury Toxins phospholipase A<sub>2</sub> venom nephrotoxicity Russell’s viper myotoxicity kidney |
| title | A Biochemical and Pharmacological Characterization of Phospholipase A<sub>2</sub> and Metalloproteinase Fractions from Eastern Russell’s Viper (<i>Daboia siamensis</i>) Venom: Two Major Components Associated with Acute Kidney Injury |
| title_full | A Biochemical and Pharmacological Characterization of Phospholipase A<sub>2</sub> and Metalloproteinase Fractions from Eastern Russell’s Viper (<i>Daboia siamensis</i>) Venom: Two Major Components Associated with Acute Kidney Injury |
| title_fullStr | A Biochemical and Pharmacological Characterization of Phospholipase A<sub>2</sub> and Metalloproteinase Fractions from Eastern Russell’s Viper (<i>Daboia siamensis</i>) Venom: Two Major Components Associated with Acute Kidney Injury |
| title_full_unstemmed | A Biochemical and Pharmacological Characterization of Phospholipase A<sub>2</sub> and Metalloproteinase Fractions from Eastern Russell’s Viper (<i>Daboia siamensis</i>) Venom: Two Major Components Associated with Acute Kidney Injury |
| title_short | A Biochemical and Pharmacological Characterization of Phospholipase A<sub>2</sub> and Metalloproteinase Fractions from Eastern Russell’s Viper (<i>Daboia siamensis</i>) Venom: Two Major Components Associated with Acute Kidney Injury |
| title_sort | biochemical and pharmacological characterization of phospholipase a sub 2 sub and metalloproteinase fractions from eastern russell s viper i daboia siamensis i venom two major components associated with acute kidney injury |
| topic | phospholipase A<sub>2</sub> venom nephrotoxicity Russell’s viper myotoxicity kidney |
| url | https://www.mdpi.com/2072-6651/13/8/521 |
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