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.
Highlights
Envenoming by kraits is a medically significant issue in South Asia and Southeast Asia
Snake venom myotoxins were reported to cause myotoxicity via plasma membrane hydrolysis and depolarization [10]. These toxins have been purified from viper, sea snake, and elapid venoms e.g. Asp49 phospholipase A2 (PLA2) myotoxin was isolated from Bothrops asper venom, PLA-H1 from Hydrophis cyanocinctus venom whereas acanmyotoxins were purified from death adder (Acanthophis sp.) venoms [8, 11,12,13]
Administration of B. candidus venoms from northeastern (BC-NE) or Bungarus candidus from southern Thailand (BC-S) venom (50 μg/kg, i.m.) significantly increased blood urea nitrogen (BUN) and potassium levels over a 3-h period when compared with 0.9% NaCl (n = 4, p < 0.05, Student’s unpaired t-test, Table 1)
Summary
Envenoming by kraits (genus Bungarus) is a medically significant issue in South Asia and Southeast Asia. There have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. 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. Snake venom myotoxins were reported to cause myotoxicity via plasma membrane hydrolysis and depolarization [10]. These toxins have been purified from viper, sea snake, and elapid venoms e.g. Asp PLA2 myotoxin was isolated from Bothrops asper venom, PLA-H1 from Hydrophis cyanocinctus venom whereas acanmyotoxins were purified from death adder (Acanthophis sp.) venoms [8, 11,12,13]
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More From: Journal of Venomous Animals and Toxins including Tropical Diseases
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