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

Abstract

BackgroundEnvenoming 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.MethodsRats 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.ResultsAdministration 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.ConclusionsThis 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.

Evaluation of the geographical utility of Eastern Russell’s viper (Daboia siamensis) antivenom from Thailand and an assessment of its protective effects against venom-induced nephrotoxicity

“…Histopathological evaluation of the kidneys of envenomed rats was determined following a previously described method [29]. Following blood collection at 12 h, all animals were sacrificed prior to kidney isolation.…”

Two Genetically Distinct yet Morphologically Indistinct Bungarus Species (Squamata, Elapidae) in Hong Kong

“…This has been documented for one B. candidus bite victim in Thailand unsuccessfully being administered anti-venom derived from a Taiwanese B. multicinctus (Warrell et al, 1983;Tan and Tan, 2015). Further complicating the issue are potential intraspecific differences in the effects of Bungarus venoms depending on geographic locality (Chaisakul et al, 2017;Charoenpitakchai et al, 2018;Laxme et al, 2019;Hia et al, 2020;Oh et al, 2021).…”

“…In Hong Kong, victims of bites by B. multicinctus, which produces some of the most potent snake venoms in the world (Gopalkrishnakone and Chou, 1992;Yin et al, 2020), are typically administered an anti-venom specifically designed for the species (Mong et al, 2017). Likewise, patients bitten by B. candidus, which also involves severe and potentially lethal consequences (Trinh et al, 2010;Chaisakul et al, 2017;Charoenpitakchai et al, 2018), are treated with species-specific anti-venoms in Thailand (Leeprasert and Kaojarern, 2007).…”

A Biochemical and Pharmacological Characterization of Phospholipase A2 and Metalloproteinase Fractions from Eastern Russell’s Viper (Daboia siamensis) Venom: Two Major Components Associated with Acute Kidney Injury

“…However, the degree of morphological changes observed in our present work could not be compared with previous work performed by our group due to the differences in species of experimental animal used and time of contact with venom or toxins. The degree of histopathologic change observed following snake envenoming is significantly associated with the time of contact with venom or toxin [ 28 ]. The effects of RvPLA 2 and RvMP on physiological function and morphological changes were abolished by the prior addition of the platelet activating factor (PAF) inhibitor, WEB 2086 [ 21 ].…”