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

 

Mongkon Charoenpitakchai¹, Kulachet Wiwatwarayos², Nattapon Jaisupa³, Muhamad Rusdi Ahmad Rusmili⁴, Supachoke Mangmool⁵, Wayne C. Hodgson⁶, Chetana Ruangpratheep¹, Lawan Chanhome⁷, Janeyuth Chaisakul³

 

1 Department 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 Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand

4 Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan Campus, Bandar Indera Mahkota, 25200 Kuantan, Pahang Darul Makmur, Malaysia

5 Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand

6 Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia

7 Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, 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: Krait; Bungarus candidus; Myotoxicity; Nephrotoxicity; Venom; Kidney

 

Received: October 18, 2017.

Accepted: March 02, 2018.

 

Correspondence: janeyuth.cha@pcm.ac.th

 

Authors' contributions

MC, KW, NJ and JC performed the experiments. LC provided B. candidus venoms used in this study. MC, KW, MRAR, and JC analyzed the data. WCH, CR, SM and JC developed the idea for the study. MC, KW, MRAR, WCH, and JC wrote the manuscript. All authors read and approved the final manuscript.

 

Competing interests

The authors declare that they have no competing interests.