Background: The common complication in cases of poisoning by Russell’s viper (Daboia siamensis) venom (RVV) is acute renal failure, but the pathogenesis involved in the alteration of kidney function is still not well understood.
Objective: To clarify the role of RVV in the pathogenesis of renal damage, the present study examines the functional short-term alterations acutely induced by RVV in isolated perfused rabbit kidney.
Methods: Effects of RVV on renal tubular handling of sodium including mean perfusion pressure (PP), the renalvascular resistance (RVR), the glomerular filtration rate (GFR), the urinary flow (V) and osmolar clearance (Cosm) were studied in two groups of isolated perfused rabbit kidneys; each group had four isolated rabbit kidneys. RVV was added to the perfusion system to obtain the final concentration of 10 ⃞g/ml.
Results: Immediate decreases in PP and RVR caused by the venom were significantly apparent (p < 0.05) in the first 15 min after RVV administration. A gradual rise in both PP and RVR occurred 15 min after the initial reduction of the first phase, but its remained below pretreatment values. The GFR, V, and Cosm decreased significantly throughout experiments after venom perfusion (p < 0.05). The total fractional sodium excretion increased significantly after venom perfusion throughout experiments, while significant reductions (p < 0.05) of renal tubular handling of sodium were apparent for proximal absolute reabsorption of sodium and proximal fractional reabsorption of sodium including marked reductions of distal absolute reabsorption of sodium and distal fractional reabsorption of sodium of the venom treated kidney. Optical microscopy of treated kidney tissue showed acute tubular necrosis at the end of experiment.
Conclusion: The present study suggests that an administration of RVV in the isolated rabbit kidney causes direct acute nephrotoxicity and acute alterations of main functional parameters that are probably mediated by either the direct action of venom components or an indirect effect from vasoactive mediators released from renal cells of the RVV-treated kidney.
1. Chaiyabutr N, Kingkheawkanthong W, Smuntavekin S, Kidmungtangdee S, Sitprija V. Renal function following Russell’s viper venom administration in dogs treated with an α-adrenergic receptor blocker, inhibitors of converting enzyme and thromboxane synthetase. J Nat Toxin. 1996; 5:389-99.
2. Sitprija V, Chaiyabutr N. Nephrotoxicity in snake envenomation. J Nat Toxin. 1999; 8:271-7.
3. Thamaree S, Sitprija V, Chaiyabutr N, Leepipatpaiboon S, Buranakarl C. Effects of intrarenal arterial infusion of russell’s viper venom on renal hemodynamics, plasma renin activity and plasma thromboxane B2 in indomethacin plus enalapril pretreated dogs. Chula Med J. 1999; 43:147-57.
4. Willinger CC, Thamaree S, Schramek H, Gstraunthaler G, Pfaller W. In vitro nephrotoxicity of Russell’s viper venom. Kidney Int. 1995; 47:518-28.
5. Ratcliffe PJ, Pukrittayakamee S, Ledingham JGG, Warrell DA. Direct nephrotoxicity of Russell’s viper venom demonstrated in the isolated perfused rat kidney. Am J Med Hyg. 1989; 40:312-9.
6. Chaiyabutr N, Sitprija V, Sugino N, Hoshi T., Russell’s viper venom-induced depolarization in the proximal tubule of Triturus kidney. Thai J Vet Med. 1985; 15: 297-303.
7. Koomans HA, Boer WH, Dorhout Mees EJ. Evaluation of lithium clearance as a marker of proximal tubule sodium handling. Kidney Inter. 1989; 36:2-12.
8. Thomsen K. Lithium clearance: a new method for determining proximal and distal tubular reabsorption of sodium and water. Nephron. 1984; 37:217-23.
9. Taft DR. The isolated perfused rat kidney model: A useful tool for drug discovery and development. Curr Drug Discov Technol. 2004; 1:97-111.
10. Tungthanathanich P. Chaiyabutr N, Sitprija V. Effect of Russell’s viper (Vipera russelli siamensis) venom on renal hemodynamics in dogs. Toxicon. 1986; 24: 365-71.
11. Young MK, Raisz LG. An anthrone procedure for determination of inulin in biological fluids. Proc Soc Exp Biol Med. 1952; 80:771-4.
12. Smith HW. Principle of renal physiology, Oxford University Press: New York, pp 196-217;1962.
13. Sitprija V, Sitprija S. Renal effects and injury induced by animal toxins. Toxicon. 2012; 60:943-53.
14. Barbosa PS, Havt A, Faco PE, Sousa TM, Bezerra IS, Fonteles MC, et al. Renal toxicity of Bothrops moojeni snake venom and its main myotoxins. Toxicon. 2002; 40:1427-35.
15. Havt A, Fonteles MC, Monteiro HS. The renal effects of Bothrops jararacussu venom and the role of PLA2 and PAF blockers. Toxicon 2001; 39:1841-6.
16. Serra H, Monteiro A, Fonteles MC.. The effect of Bothrops jararaca venom on rat kidney after shortterm exposure: preliminary results. Pharmacol Toxicol. 1999; 85:198-200.
17. Monteiro HS, da Silva IM, Martins AM, Fonteles MC. Actions of Crotalus durissus terrificus venom and crotoxin on the isolated rat kidney. Braz J Med Biol Res. 2001; 34:1347-52.
18. Cupples W, Loutzenhiser R. Dynamic autoregulation in the in vitro perfused hydronephrotic rat kidney. Am J Physiol. 1998; 275:F126-30.
19. Buranakarl C, Kalandakanon S, Komolvanich S, Chaiyabutr N. Inhibition of the renal Na-K-ATPase by Russell’s viper venom. Thai J Physiol. Sci. 1997; 10:27-36.
20. Sitprija V. Snakebite nephropathy. Nephrology. 2006; 11:442-8.