Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand

Mongkon Charoenpitakchai, Kulachet Wiwatwarayos, Nattapon Jaisupa, Muhamad Rusdi Ahmad Rusmili, Supachoke Mangmool, Wayne C. Hodgson, Chetana Ruangpratheep, Lawan Chanhome, Janeyuth Chaisakul

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Envenoming by kraits (genus Bungarus) is a medically significant issue in South Asia and Southeast Asia. Malayan krait (Bungarus candidus) venom is known to contain highly potent neurotoxins. In recent years, there have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. However, research on such non-neurotoxicity activities of Malayan krait venom is extremely limited. Thus, the aim of the present study was to determine the myotoxic, cytotoxic and nephrotoxic activities of B. candidus venoms from northeastern (BC-NE) and southern (BC-S) Thailand in experimentally envenomed rats. Methods: Rats were administered Malayan krait (BC-NE or BC-S) venom (50 μg/kg, i.m.) or 0.9% NaCl solution (50 μL, i.m.) into the right hind limb. The animals were sacrificed 3, 6 and 24 h after venom administration. The right gastrocnemius muscle and both kidneys were collected for histopathological analysis. Blood samples were also taken for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) levels. The human embryonic kidney cell line (HEK-293) was used in a cell proliferation assay to determine cytotoxic activity. Results: Administration of BC-NE or BC-S venom (50 μg/kg, i.m.) caused time-dependent myotoxicity, characterized by an elevation of CK and LDH levels. Histopathological examination of skeletal muscle displayed marked muscle necrosis and myofiber disintegration 24 h following venom administration. Both Malayan krait venoms also induced extensive renal tubular injury with glomerular and interstitial congestion in rats. BC-NE and BC-S venoms (100-0.2 μg/mL) caused concentration-dependent cytotoxicity on the HEK-293 cell line. However, BC-NE venom (IC50 = 8 ± 1 μg/mL; at 24 h incubation; n = 4) was found to be significantly more cytotoxic than BC-S venom (IC50 = 15 ± 2 μg/mL; at 24 h incubation; n = 4). In addition, the PLA2 activity of BC-NE venom was significantly higher than that of BC-S venom. Conclusions: This study found that Malayan krait venoms from both populations possess myotoxic, cytotoxic and nephrotoxic activities. These findings may aid in clinical diagnosis and treatment of envenomed patients in the future.

Original languageEnglish
Article number9
Number of pages9
JournalJournal of Venomous Animals and Toxins Including Tropical Diseases
Volume24
Issue number1
DOIs
Publication statusPublished - 9 Mar 2018

Keywords

  • Bungarus candidus
  • Kidney
  • Krait
  • Myotoxicity
  • Nephrotoxicity
  • Venom

Cite this

Charoenpitakchai, Mongkon ; Wiwatwarayos, Kulachet ; Jaisupa, Nattapon ; Rusmili, Muhamad Rusdi Ahmad ; Mangmool, Supachoke ; Hodgson, Wayne C. ; Ruangpratheep, Chetana ; Chanhome, Lawan ; Chaisakul, Janeyuth. / Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand. In: Journal of Venomous Animals and Toxins Including Tropical Diseases. 2018 ; Vol. 24, No. 1.
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title = "Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand",
abstract = "Background: Envenoming by kraits (genus Bungarus) is a medically significant issue in South Asia and Southeast Asia. Malayan krait (Bungarus candidus) venom is known to contain highly potent neurotoxins. In recent years, there have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. However, research on such non-neurotoxicity activities of Malayan krait venom is extremely limited. Thus, the aim of the present study was to determine the myotoxic, cytotoxic and nephrotoxic activities of B. candidus venoms from northeastern (BC-NE) and southern (BC-S) Thailand in experimentally envenomed rats. Methods: Rats were administered Malayan krait (BC-NE or BC-S) venom (50 μg/kg, i.m.) or 0.9{\%} NaCl solution (50 μL, i.m.) into the right hind limb. The animals were sacrificed 3, 6 and 24 h after venom administration. The right gastrocnemius muscle and both kidneys were collected for histopathological analysis. Blood samples were also taken for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) levels. The human embryonic kidney cell line (HEK-293) was used in a cell proliferation assay to determine cytotoxic activity. Results: Administration of BC-NE or BC-S venom (50 μg/kg, i.m.) caused time-dependent myotoxicity, characterized by an elevation of CK and LDH levels. Histopathological examination of skeletal muscle displayed marked muscle necrosis and myofiber disintegration 24 h following venom administration. Both Malayan krait venoms also induced extensive renal tubular injury with glomerular and interstitial congestion in rats. BC-NE and BC-S venoms (100-0.2 μg/mL) caused concentration-dependent cytotoxicity on the HEK-293 cell line. However, BC-NE venom (IC50 = 8 ± 1 μg/mL; at 24 h incubation; n = 4) was found to be significantly more cytotoxic than BC-S venom (IC50 = 15 ± 2 μg/mL; at 24 h incubation; n = 4). In addition, the PLA2 activity of BC-NE venom was significantly higher than that of BC-S venom. Conclusions: This study found that Malayan krait venoms from both populations possess myotoxic, cytotoxic and nephrotoxic activities. These findings may aid in clinical diagnosis and treatment of envenomed patients in the future.",
keywords = "Bungarus candidus, Kidney, Krait, Myotoxicity, Nephrotoxicity, Venom",
author = "Mongkon Charoenpitakchai and Kulachet Wiwatwarayos and Nattapon Jaisupa and Rusmili, {Muhamad Rusdi Ahmad} and Supachoke Mangmool and Hodgson, {Wayne C.} and Chetana Ruangpratheep and Lawan Chanhome and Janeyuth Chaisakul",
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doi = "10.1186/s40409-018-0146-y",
language = "English",
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Charoenpitakchai, M, Wiwatwarayos, K, Jaisupa, N, Rusmili, MRA, Mangmool, S, Hodgson, WC, Ruangpratheep, C, Chanhome, L & Chaisakul, J 2018, 'Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand' Journal of Venomous Animals and Toxins Including Tropical Diseases, vol. 24, no. 1, 9. https://doi.org/10.1186/s40409-018-0146-y

Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand. / Charoenpitakchai, Mongkon; Wiwatwarayos, Kulachet; Jaisupa, Nattapon; Rusmili, Muhamad Rusdi Ahmad; Mangmool, Supachoke; Hodgson, Wayne C.; Ruangpratheep, Chetana; Chanhome, Lawan; Chaisakul, Janeyuth.

In: Journal of Venomous Animals and Toxins Including Tropical Diseases, Vol. 24, No. 1, 9, 09.03.2018.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand

AU - Charoenpitakchai, Mongkon

AU - Wiwatwarayos, Kulachet

AU - Jaisupa, Nattapon

AU - Rusmili, Muhamad Rusdi Ahmad

AU - Mangmool, Supachoke

AU - Hodgson, Wayne C.

AU - Ruangpratheep, Chetana

AU - Chanhome, Lawan

AU - Chaisakul, Janeyuth

PY - 2018/3/9

Y1 - 2018/3/9

N2 - Background: Envenoming by kraits (genus Bungarus) is a medically significant issue in South Asia and Southeast Asia. Malayan krait (Bungarus candidus) venom is known to contain highly potent neurotoxins. In recent years, there have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. However, research on such non-neurotoxicity activities of Malayan krait venom is extremely limited. Thus, the aim of the present study was to determine the myotoxic, cytotoxic and nephrotoxic activities of B. candidus venoms from northeastern (BC-NE) and southern (BC-S) Thailand in experimentally envenomed rats. Methods: Rats were administered Malayan krait (BC-NE or BC-S) venom (50 μg/kg, i.m.) or 0.9% NaCl solution (50 μL, i.m.) into the right hind limb. The animals were sacrificed 3, 6 and 24 h after venom administration. The right gastrocnemius muscle and both kidneys were collected for histopathological analysis. Blood samples were also taken for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) levels. The human embryonic kidney cell line (HEK-293) was used in a cell proliferation assay to determine cytotoxic activity. Results: Administration of BC-NE or BC-S venom (50 μg/kg, i.m.) caused time-dependent myotoxicity, characterized by an elevation of CK and LDH levels. Histopathological examination of skeletal muscle displayed marked muscle necrosis and myofiber disintegration 24 h following venom administration. Both Malayan krait venoms also induced extensive renal tubular injury with glomerular and interstitial congestion in rats. BC-NE and BC-S venoms (100-0.2 μg/mL) caused concentration-dependent cytotoxicity on the HEK-293 cell line. However, BC-NE venom (IC50 = 8 ± 1 μg/mL; at 24 h incubation; n = 4) was found to be significantly more cytotoxic than BC-S venom (IC50 = 15 ± 2 μg/mL; at 24 h incubation; n = 4). In addition, the PLA2 activity of BC-NE venom was significantly higher than that of BC-S venom. Conclusions: This study found that Malayan krait venoms from both populations possess myotoxic, cytotoxic and nephrotoxic activities. These findings may aid in clinical diagnosis and treatment of envenomed patients in the future.

AB - Background: Envenoming by kraits (genus Bungarus) is a medically significant issue in South Asia and Southeast Asia. Malayan krait (Bungarus candidus) venom is known to contain highly potent neurotoxins. In recent years, there have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. However, research on such non-neurotoxicity activities of Malayan krait venom is extremely limited. Thus, the aim of the present study was to determine the myotoxic, cytotoxic and nephrotoxic activities of B. candidus venoms from northeastern (BC-NE) and southern (BC-S) Thailand in experimentally envenomed rats. Methods: Rats were administered Malayan krait (BC-NE or BC-S) venom (50 μg/kg, i.m.) or 0.9% NaCl solution (50 μL, i.m.) into the right hind limb. The animals were sacrificed 3, 6 and 24 h after venom administration. The right gastrocnemius muscle and both kidneys were collected for histopathological analysis. Blood samples were also taken for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) levels. The human embryonic kidney cell line (HEK-293) was used in a cell proliferation assay to determine cytotoxic activity. Results: Administration of BC-NE or BC-S venom (50 μg/kg, i.m.) caused time-dependent myotoxicity, characterized by an elevation of CK and LDH levels. Histopathological examination of skeletal muscle displayed marked muscle necrosis and myofiber disintegration 24 h following venom administration. Both Malayan krait venoms also induced extensive renal tubular injury with glomerular and interstitial congestion in rats. BC-NE and BC-S venoms (100-0.2 μg/mL) caused concentration-dependent cytotoxicity on the HEK-293 cell line. However, BC-NE venom (IC50 = 8 ± 1 μg/mL; at 24 h incubation; n = 4) was found to be significantly more cytotoxic than BC-S venom (IC50 = 15 ± 2 μg/mL; at 24 h incubation; n = 4). In addition, the PLA2 activity of BC-NE venom was significantly higher than that of BC-S venom. Conclusions: This study found that Malayan krait venoms from both populations possess myotoxic, cytotoxic and nephrotoxic activities. These findings may aid in clinical diagnosis and treatment of envenomed patients in the future.

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KW - Kidney

KW - Krait

KW - Myotoxicity

KW - Nephrotoxicity

KW - Venom

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