Résumé
Abstract Background: This study examines the direct nephrotoxic effects of Daboia siamensis venom (RVV) and venom fractions in in vivo and isolated perfused kidneys (IPK) to understand the role of inflammation pathways and susceptibility to oxidative stress in venom or fraction-induced acute renal failure. Methods: We administered RVV and its venom fractions (PLA2, MP, LAAO, and PDE) to rabbits in vivo and in the IPK model. We measured oxidative stress biomarkers (SOD, CAT, GSH, and MDA) in kidney tissue, as well as inflammatory cytokines (TNF-α, IL-1β, IFN-γ, IL-4, IL-5, and IL-10), MDA and GSH levels in plasma and urine. We also calculated fractional excretion (FE) for pro-/anti-inflammatory cytokines and oxidative stress biomarkers, including the ratios of pro-/anti-inflammatory cytokines in urine after envenomation. Results: In both kidney models, significant increases in MDA, SOD, CAT, and GSH levels were observed in kidney tissues, along with elevated concentrations of MDA and GSH in plasma and urine after injecting RVV and venom fractions. Moreover, RVV injections led to progressive increases in FEMDA and decreases in FEGSH. The concentrations of IL-4, IL-5, IL-10, IFN-γ, and TNF-α in plasma increased in vivo, as well as in the urine of the IPK model, but not for IL-1β in both plasma and urine after RVV administrations. Urinary fractional excretion of TNF-α, IL-1β, IFN-γ, IL-4, IL-5, and IL-10 tended to decrease in vivo but showed elevated levels in the IPK model. A single RVV injection in vivo disrupted the balance of urinary cytokines, significantly reducing either the TNF-α/IL-10 ratio or the IFN-γ/IL-10 ratio. Conclusion: RVV induces renal tubular toxicity by increasing oxidative stress production and elevating inflammatory cytokines in urine. During the acute phase of acute kidney injury, the balance of urine cytokines shifts toward anti-inflammatory dominance within the first two hours post-RVV and venom fractions.
Résumé
Background: Envenoming by snakebite is an important public health problem in rural tropics. Venomous snake families such as Elapidae and Viperidae frequently produce severe poisoning. Anti-venoms are not available for all venomous snakes of Thailand and there is need for more development in this field. Objective: We characterized the important venomous snakes’ distribution of Thailand. Method: Venomous snake species are described in details including their identification, range, and extraterritorial distribution. Result: Eighteen snake species of the family Elapidae are summarized in their characteristics and distribution. There are three species of Naja, one species of Ophiophagus, three species of Bungarus, four species of Calliophis, one species of Sinomicrurus, two species of Laticauda, and four species of subfamily Hydrophiinae. Fifteen snake species of the family Viperidae consisting of one species of subfamily Viperinae and fourteen species of subfamily Crotalinae are also discussed. Conclusion: All these snakes are venomous and their venom is potentially fatal since birth.
Résumé
Background: Many studies have reported the occurrence of lethal acute renal failure after snakebites. Bungarus candidus (Malayan krait) is a medically important venomous snake distributed widely throughout Southeast Asia. The best known features of systemic envenoming by B. candidus are neurotoxic. Objective: Obtain more information on effects of B. candidus venom on changes in systemic and renal hemodynamics in experimental animals. Methods: Twelve adult male New Zealand white rabbits were used to study the effect of B. candidus venom on general circulation and renal hemodynamics. An anesthetized animal was intravenously injected with B. candidus venom at a dosage of 50μg/kg bodyweight. All changes of parameters were observed after initial post venom injection and recorded at 30 min intervals until 150 minutes after envenomation. Results: After envenomation, cardiovascular responses showed a marked decrease in mean arterial pressure within two minutes, afterwards gradually returning closely to baseline values. There were stepwise decreases in heart rate and cardiac output, while total peripheral resistance was slightly increased. The renal hemodynamics significantly decreased by glomerular filtration rate, effective renal plasma flow and effective renal blood flow, while the filtration fraction significantly increased. Envenomed animals showed a reduction in renal fraction, while renal vascular resistance stepwise increased. The plasma potassium level tended to increase. Animals showed stepwise decreases in urinary excretion of Na+, K+ and Cl-. A marked decrease in plasma calcium level was apparent at 120 minutes, while plasma creatine phosphokinase and lactate dehydrogenase levels increased at 30-120 minutes. Conclusion: A significant drop in blood pressure was attributed to a sustained fall in cardiac output, which would be associated with a reduction in heart rate. Sustained hypotension would contribute to reduction of renal blood flow, which results in decreased GFR.
Résumé
OBJECTIVE: To study the mechanism(s) of acute hypercalcemia-induced hypertension in dogs. MATERIAL AND METHOD: Adult male mongrel dogs were intravenously infused with: 1) normal saline solution, 2) CaCl2 solution, 3) CaCl2 + calcium channel blocker (verapamil), 4) CaCl2 + selective alpha-1 adrenergic receptor blocker (prazosin), or 5) CaCl2 + verapamil + prazosin. Either verapamil or prazosin treatment was started at forty minutes before CaCl2 infusion and then was co-administered throughout the three-hour experimental period. Systemic and renal hemodynamics parameters were determined. RESULTS: Infusion of CaCl2 caused increases in mean arterial blood pressure (p < 0.01), total peripheral resistance (p < 0.001), and renal vascular resistance (p < 0.001). Prior treatment with either verapamil or prazosin lowered baseline blood pressure (p < 0.01) and could prevent hypercalcemia-induced hypertension. This occurred accompanying regaining to near normal values of abnormal systemic hemodynamics parameters. Combination of both drugs showed more profound effects, particularly on lowering renal vascular resistance. CONCLUSION: Acute hypercalemic hypertension is caused by an increase in vascular resistance mediated via the direct effect of calcium on vascular smooth muscle as well as the indirect effect of calcium induced hypercatecholaminemia. The stimulatory effect of hypercalcemia on renal vascular resistance is more prominent than that on peripheral vascular resistance.