ObjectiveTo examine the efficiency of hemoperfusion in removing South American rattlesnake (Crotalus durissus terrificus) venom from rats compared with neutralization by antivenom.DesignAn exploratory experimental investigation in rats involving the injection of snake venom with or without subsequent hemoperfusion or antivenom administration.SettingBasic animal research laboratory in a private university.AnimalsNormal, healthy male Wistar rats (0.29‐0.40 kg, 3‐6 months old) from a commercial breeder.InterventionsFour experimental groups of randomly allocated rats (n = 3/group) were studied: Group 1: rats were injected with a single dose of venom (5 mg/kg, IM, in the right thigh) with no other treatment; blood samples were collected minutes before death to determine leukocyte, platelet, and erythrocyte counts; Group 2 (Control): rats underwent hemoperfusion alone for 60 min using a hemoperfusion cartridge designed for protein adsorption (by granulated charcoal) and protein precipitation (by tannic acid); Group 3 (Venom + antivenom): rats were injected with venom (5 mg/kg, IM) and, 10 min later, were treated with antivenom at the venom:antivenom ratio recommended by the manufacturer; Group 4 (Venom + hemoperfusion): Rats were injected with venom (5 mg/kg, IM) and, 10 min later, were hemoperfused for 60 min. In groups 2‐4, blood samples were collected for leukocyte, platelet, and erythrocyte counts 24 h after venom.Measurements and Main ResultsRats injected with venom alone (Group 1) developed signs of neurotoxicity and ataxia and died in 9.0 ± 0.43 h but showed no changes in leukocyte or erythrocyte counts. In contrast, there were no deaths in groups 2‐4. The lack of deaths in Groups 3 and 4 indicated that antivenom and hemoperfusion, respectively, protected against the lethal effects of the venom.ConclusionsHemoperfusion with a double‐action hemoperfusion cartridge capable of protein adsorption and precipitation protected rats against C. d. terrificus venom.

We examined the ability of Bothrops jararaca venom (12.5 mg/kg) injected intraperitoneally (i.p.) to cause acute kidney injury (AKI) in rats. Blood urea and creatinine (AKI biomarkers, in g dL -1 ) were elevated after 2 h in venom-treated rats (urea: from 0.41±0.1 to 0.7±0.03; creatinine from 46.7±3.1 to 85±6.7; p<0.05; n=3 each), with no change in circulating reduced glutathione. Venom-treated rats survived for ~6 h, at which point platelets were reduced (x10 3 µL -1 ; from 763.8±30.2 to 52.5±18.2) whereas leukocytes and erythrocytes were slightly increased (from 4.7±0.3 to 6.6±0.1 x 10 3 µL -1 and from 8.38±0.1 to 9.2±0.09 x 10 6 µL -1 , respectively; p<0.05); blood protein (5.2±0.4 g dL -1 ) and albumin (2.7±0.1 g dL -1 ) were normal, whereas blood and urinary urea and creatinine were increased. All parameters returned to normal with antivenom given 2 h post-envenomation. The i.p. injection of venom caused AKI similar to that seen with other routes of administration.

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In this work, the potential usefulness of silver nanoparticles (AgNPs) for treating burn wounds was examined. Methods: Second-degree burns were induced in male Wistar rats by touching the skin with a heated (70°C) metallic device for 10 s, after which the animals were randomly allocated to one of two groups: control (n=8, treated with sterile saline) and experimental (n=8, treated with AgNPs, 0.081 mg/mL; 50 µL applied to the burn surface). Seven, 14, 21 and 28 days after lesion induction two rats from each group were killed and blood samples were collected for a complete blood count and to assess oxidative stress. The livers were examined macroscopically and skin samples were collected for histological analysis. Results: Macroscopically, wound healing and skin remodeling in the experimental group were similar to the saline-treated rats. Likewise, there were no significant differences in the histological parameters between the two groups. However, treatment with AgNPs caused a persistent reduction in white blood cell (WBC) counts throughout the experiment, whereas platelet counts increased on days 7 and 28 but decreased on days 14 and 21; there was also an increase in the blood concentration of reduced glutathione on day 7 followed by a decrease on days 21 and 28. There were no significant changes in blood glutathione peroxidase (GSH-Px) and catalase (CAT) activities or in the serum concentration of thiobarbituric acid reactive substances. Conclusion: The findings of this study raise questions about the potential transitory effects of AgNPs based on the changes in WBC and platelet counts, blood glutathione concentrations and macroscopic hepatic alterations.

Systemic envenomation by Crotalus durissus terrificus (South American rattlesnake) can cause coagulopathy, rabdomyolysis, acute kidney injury, and peripheral neuromuscular blockade, the latter resulting in flaccid paralysis. Previous studies have shown that plant products such as tannic acid and theaflavin can protect against the neuromuscular blockade caused by C. d. terrificus venom in vitro. In this work, we used mouse-isolated phrenic nerve-diaphragm preparations to examine the ability of caffeic acid, chlorogenic acid, and quercetin to protect against C. d. terrificus venom-induced neuromuscular blockade in vitro. In addition, the ability of tannic acid to protect against the systemic effects of severe envenomation was assessed in rats. Preincubation of venom with caffeic acid (0.5 mg/mL), chlorogenic acid (1 mg/mL), or quercetin (0.5 mg/mL) failed to protect against venom (10 μg/mL)-induced neuromuscular blockade. In rats, venom (6 mg kg−1, i.p.) caused death in ~8 h, which was prevented by preincubation of venom with tannic acid or the administration of antivenom 2 h post-venom, whereas tannic acid given 2 h post-venom prolonged survival (~18.5 h) but did not prevent death. Tannic acid (in preincubation protocols or given 2 h post-venom) had a variable effect on blood creatinine and urea and blood/urine protein levels and prevented venom-induced leukocytosis. Tannic acid attenuated the histological lesions associated with renal damage in a manner similar to antivenom. The protective effect of tannic acid appeared to be mediated by interaction with venom proteins, as assessed by SDS-PAGE. These findings suggest that tannic acid could be a potentially useful ancillary treatment for envenomation by C. d. terrificus.