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

Journal of venomous animals and toxins

Kulachet Wiwatwarayos^2¹  Mongkon Charoenpitakchai^1²  Supachoke Mangmool^5³  Lawan Chanhome^7⁴  Nattapon Jaisupa^3⁵  Muhamad Rusdi Ahmad Rusmili^4⁶  Wayne C. Hodgson^6⁷  Chetana Ruangpratheep^1⁸ 

[1] Department of Anatomical Pathology, Army Institute of Pathology, Royal Thai Army Medical Department, Bangkok, 10400 Thailand^2;Department of Pathology, Phramongkutklao College of Medicine, Bangkok, 10400 Thailand^1;Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, 10400 Thailand^5;Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok, 10400 Thailand Find articles by Janeyuth Chaisakul^8;Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok, 10400 Thailand^3;Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan Campus, Bandar Indera Mahkota, 25200 Kuantan, Pahang Darul Makmur Malaysia^4;Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800 Australia^6;Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok, 10330 Thailand^7

关键词: Krait;    Bungarus candidus;    Myotoxicity;    Nephrotoxicity;    Venom;    Kidney;   

DOI  :  10.1186/s40409-018-0146-y

学科分类：药理学

来源: BioMed Central

【 摘 要 】

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.

【 授权许可】

CC BY