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

Charoenpitakchai M 1 , Wiwatwarayos K 2 , Jaisupa N 3 , Rusmili MRA 4 , Mangmool S 5 , Hodgson WC 6 Show all authors , Ruangpratheep C 1 , Chanhome L 7 , Chaisakul J 3

Affiliations 

  • 1 1Department of Pathology, Phramongkutklao College of Medicine, Bangkok, 10400 Thailand
  • 2 Department of Anatomical Pathology, Army Institute of Pathology, Royal Thai Army Medical Department, Bangkok, 10400 Thailand
  • 3 3Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok, 10400 Thailand
  • 4 4Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan Campus, Bandar Indera Mahkota, 25200 Kuantan, Pahang Darul Makmur Malaysia
  • 5 5Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, 10400 Thailand
  • 6 6Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800 Australia
  • 7 7Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok, 10330 Thailand
J Venom Anim Toxins Incl Trop Dis, 2018;24:9.
PMID: 29556251 DOI: 10.1186/s40409-018-0146-y

Abstract

Background: Envenoming by kraits (genusBungarus) 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 ofB. candidusvenoms 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 PLA2activity 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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