Comparative Analysis of the Enzymatic, Coagulant, and Neuromuscular Activities of Two Variants of <i>Crotalus durissus ruruima</i> Venom and Antivenom Efficacy
<b>Background:</b> We compared the enzymatic, coagulant, and neuromuscular activities of two variants (yellow—CDRy and white—CDRw) of <i>Crotalus durissus ruruima</i> venom with a sample of <i>C. d. terrificus</i> (CDT) venom and examined their neutralization by a...
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| author | Poliana J. Demico Isabele N. Oliveira Vitória S. Proença-Hirata Samuel R. Dias Hugo A. Ghirotti Elisangela O. Silva Inês C. Giometti Francis L. Pacagnelli Kristian A. Torres-Bonilla Stephen Hyslop Nathália C. Galizio Karen de Morais-Zani Manuela B. Pucca Anderson M. Rocha Jéssica B. Maciel Marco A. Sartim Wuelton M. Monteiro Rafael S. Floriano |
| author_facet | Poliana J. Demico Isabele N. Oliveira Vitória S. Proença-Hirata Samuel R. Dias Hugo A. Ghirotti Elisangela O. Silva Inês C. Giometti Francis L. Pacagnelli Kristian A. Torres-Bonilla Stephen Hyslop Nathália C. Galizio Karen de Morais-Zani Manuela B. Pucca Anderson M. Rocha Jéssica B. Maciel Marco A. Sartim Wuelton M. Monteiro Rafael S. Floriano |
| author_sort | Poliana J. Demico |
| collection | DOAJ |
| description | <b>Background:</b> We compared the enzymatic, coagulant, and neuromuscular activities of two variants (yellow—CDRy and white—CDRw) of <i>Crotalus durissus ruruima</i> venom with a sample of <i>C. d. terrificus</i> (CDT) venom and examined their neutralization by antivenom against CDT venom. <b>Methods:</b> The venoms were screened for enzymatic and coagulant activities using standard assays, and electrophoretic profiles were compared by SDS-PAGE. Neutralization was assessed by preincubating venoms with crotalic antivenom and assaying the residual activity. <b>Results:</b> SDS-PAGE showed that the venoms had similar electrophoretic profiles, with the main bands being phospholipase A<sub>2</sub> (PLA<sub>2</sub>), serine proteinases, L-amino acid oxidase (LAAO), and phosphodiesterase. CDRy venom had the highest proteolytic and LAAO activities, CDRw venom had greater PLA<sub>2</sub> and esterolytic activities at the highest quantity tested, and CDT had greater PLA<sub>2</sub> activity than CDRy. CDRw and CDT venoms had similar proteolytic and LAAO activities, and CDRy and CDT venoms had comparable esterolytic activity. None of the venoms altered the prothrombin time (PT), but all of them decreased the activated partial thromboplastin time (aPPT); this activity was neutralized by antivenom. The minimum coagulant dose potency was CDRw >> CDRy > CDT. All venoms had thrombin-like activity that was attenuated by antivenom. CDRy and CDRw venoms showed α-fibrinogenolytic activity. All venoms partially cleaved the β-chain. CDRy and CDT venoms caused neuromuscular facilitation (enhanced muscle contractions) followed by complete blockade, whereas CDRw venom caused only blockade. Antivenom neutralized the neuromuscular activity to varying degrees. <b>Conclusions:</b> These findings indicate that while CDR and CDT venoms share similarities, they also differ in some enzymatic and biological activities and in neutralization by antivenom. Some of these differences could influence the clinical manifestations of envenomation by <i>C. d. ruruima</i> and their neutralization by the currently used therapeutic antivenom. |
| format | Article |
| id | doaj-art-aa3d2587cac24d469b89b188a6d0272c |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | Pharmaceuticals |
| spelling | doaj-art-aa3d2587cac24d469b89b188a6d0272c2025-01-24T13:45:12ZengMDPI AGPharmaceuticals1424-82472025-01-011815410.3390/ph18010054Comparative Analysis of the Enzymatic, Coagulant, and Neuromuscular Activities of Two Variants of <i>Crotalus durissus ruruima</i> Venom and Antivenom EfficacyPoliana J. Demico0Isabele N. Oliveira1Vitória S. Proença-Hirata2Samuel R. Dias3Hugo A. Ghirotti4Elisangela O. Silva5Inês C. Giometti6Francis L. Pacagnelli7Kristian A. Torres-Bonilla8Stephen Hyslop9Nathália C. Galizio10Karen de Morais-Zani11Manuela B. Pucca12Anderson M. Rocha13Jéssica B. Maciel14Marco A. Sartim15Wuelton M. Monteiro16Rafael S. Floriano17Laboratory of Toxinology and Cardiovascular Research, University of Western São Paulo (UNOESTE), Presidente Prudente 19050-680, SP, BrazilLaboratory of Toxinology and Cardiovascular Research, University of Western São Paulo (UNOESTE), Presidente Prudente 19050-680, SP, BrazilLaboratory of Toxinology and Cardiovascular Research, University of Western São Paulo (UNOESTE), Presidente Prudente 19050-680, SP, BrazilLaboratory of Toxinology and Cardiovascular Research, University of Western São Paulo (UNOESTE), Presidente Prudente 19050-680, SP, BrazilLaboratory of Toxinology and Cardiovascular Research, University of Western São Paulo (UNOESTE), Presidente Prudente 19050-680, SP, BrazilLaboratory of Toxinology and Cardiovascular Research, University of Western São Paulo (UNOESTE), Presidente Prudente 19050-680, SP, BrazilLaboratory of Toxinology and Cardiovascular Research, University of Western São Paulo (UNOESTE), Presidente Prudente 19050-680, SP, BrazilLaboratory of Toxinology and Cardiovascular Research, University of Western São Paulo (UNOESTE), Presidente Prudente 19050-680, SP, BrazilDepartment of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas 13083-888, SP, BrazilDepartment of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas 13083-888, SP, BrazilLaboratory of Pathophysiology, Butantan Institute, São Paulo 05585-000, SP, BrazilLaboratory of Pathophysiology, Butantan Institute, São Paulo 05585-000, SP, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, BrazilGraduate Program in Tropical Medicine, State University of Amazonas (UEA), Manaus 69850-000, AM, BrazilGraduate Program in Tropical Medicine, State University of Amazonas (UEA), Manaus 69850-000, AM, BrazilGraduate Program in Tropical Medicine, State University of Amazonas (UEA), Manaus 69850-000, AM, BrazilGraduate Program in Tropical Medicine, State University of Amazonas (UEA), Manaus 69850-000, AM, BrazilLaboratory of Toxinology and Cardiovascular Research, University of Western São Paulo (UNOESTE), Presidente Prudente 19050-680, SP, Brazil<b>Background:</b> We compared the enzymatic, coagulant, and neuromuscular activities of two variants (yellow—CDRy and white—CDRw) of <i>Crotalus durissus ruruima</i> venom with a sample of <i>C. d. terrificus</i> (CDT) venom and examined their neutralization by antivenom against CDT venom. <b>Methods:</b> The venoms were screened for enzymatic and coagulant activities using standard assays, and electrophoretic profiles were compared by SDS-PAGE. Neutralization was assessed by preincubating venoms with crotalic antivenom and assaying the residual activity. <b>Results:</b> SDS-PAGE showed that the venoms had similar electrophoretic profiles, with the main bands being phospholipase A<sub>2</sub> (PLA<sub>2</sub>), serine proteinases, L-amino acid oxidase (LAAO), and phosphodiesterase. CDRy venom had the highest proteolytic and LAAO activities, CDRw venom had greater PLA<sub>2</sub> and esterolytic activities at the highest quantity tested, and CDT had greater PLA<sub>2</sub> activity than CDRy. CDRw and CDT venoms had similar proteolytic and LAAO activities, and CDRy and CDT venoms had comparable esterolytic activity. None of the venoms altered the prothrombin time (PT), but all of them decreased the activated partial thromboplastin time (aPPT); this activity was neutralized by antivenom. The minimum coagulant dose potency was CDRw >> CDRy > CDT. All venoms had thrombin-like activity that was attenuated by antivenom. CDRy and CDRw venoms showed α-fibrinogenolytic activity. All venoms partially cleaved the β-chain. CDRy and CDT venoms caused neuromuscular facilitation (enhanced muscle contractions) followed by complete blockade, whereas CDRw venom caused only blockade. Antivenom neutralized the neuromuscular activity to varying degrees. <b>Conclusions:</b> These findings indicate that while CDR and CDT venoms share similarities, they also differ in some enzymatic and biological activities and in neutralization by antivenom. Some of these differences could influence the clinical manifestations of envenomation by <i>C. d. ruruima</i> and their neutralization by the currently used therapeutic antivenom.https://www.mdpi.com/1424-8247/18/1/54<i>Crotalus durissus</i> venomcoagulant activityenzymatic activityintraspecific variationneurotoxicityneutralization by antivenom |
| spellingShingle | Poliana J. Demico Isabele N. Oliveira Vitória S. Proença-Hirata Samuel R. Dias Hugo A. Ghirotti Elisangela O. Silva Inês C. Giometti Francis L. Pacagnelli Kristian A. Torres-Bonilla Stephen Hyslop Nathália C. Galizio Karen de Morais-Zani Manuela B. Pucca Anderson M. Rocha Jéssica B. Maciel Marco A. Sartim Wuelton M. Monteiro Rafael S. Floriano Comparative Analysis of the Enzymatic, Coagulant, and Neuromuscular Activities of Two Variants of <i>Crotalus durissus ruruima</i> Venom and Antivenom Efficacy Pharmaceuticals <i>Crotalus durissus</i> venom coagulant activity enzymatic activity intraspecific variation neurotoxicity neutralization by antivenom |
| title | Comparative Analysis of the Enzymatic, Coagulant, and Neuromuscular Activities of Two Variants of <i>Crotalus durissus ruruima</i> Venom and Antivenom Efficacy |
| title_full | Comparative Analysis of the Enzymatic, Coagulant, and Neuromuscular Activities of Two Variants of <i>Crotalus durissus ruruima</i> Venom and Antivenom Efficacy |
| title_fullStr | Comparative Analysis of the Enzymatic, Coagulant, and Neuromuscular Activities of Two Variants of <i>Crotalus durissus ruruima</i> Venom and Antivenom Efficacy |
| title_full_unstemmed | Comparative Analysis of the Enzymatic, Coagulant, and Neuromuscular Activities of Two Variants of <i>Crotalus durissus ruruima</i> Venom and Antivenom Efficacy |
| title_short | Comparative Analysis of the Enzymatic, Coagulant, and Neuromuscular Activities of Two Variants of <i>Crotalus durissus ruruima</i> Venom and Antivenom Efficacy |
| title_sort | comparative analysis of the enzymatic coagulant and neuromuscular activities of two variants of i crotalus durissus ruruima i venom and antivenom efficacy |
| topic | <i>Crotalus durissus</i> venom coagulant activity enzymatic activity intraspecific variation neurotoxicity neutralization by antivenom |
| url | https://www.mdpi.com/1424-8247/18/1/54 |
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