Clinical effects of immunization, bleeding, and albumin-based fluid therapy in horses used as immunoglobulin source to produce a polyspecific antivenom (Echitab-plus-ICP) towards venoms of African snakes

IF 3.6 Q2 TOXICOLOGY Toxicon: X Pub Date : 2023-06-01 DOI:10.1016/j.toxcx.2023.100158
Rose Mary Huertas , Mauricio Arguedas , Juan Manuel Estrada , Edwin Moscoso , Deibid Umaña , Gabriela Solano , Mariángela Vargas , Álvaro Segura , Andrés Sánchez , María Herrera , Mauren Villalta , Cynthia Arroyo-Portilla , José María Gutiérrez , Guillermo León
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Abstract

During the production of snake antivenoms, the animals used as immunoglobulin source are subjected to processes that could deteriorate their physical condition. Therefore, these conditions must be carefully designed and validated. In this work, the immunization and bleeding protocols applied to horses used to produce the African polyspecific antivenom EchiTAb-plus-ICP were evaluated regarding their effects on the horses' health. The study focused on horses that had been previously immunized with venoms and then received periodic booster venom injections for antivenom production. It was found that the periodic immunization with 5 mg of a mixture of venoms of Bitis arietans, Echis ocellatus, Dendroaspis polylepis, and Naja nigricollis did not induce systemic signs of envenomation, and only caused mild swelling at the injection site, which did not evolve to abscesses, fistulas, or fibrosis. Three consecutive days of bleeding, collecting 6–8 L of blood per day, and self-transfusing the red blood cells (RBC) in the second and third days, did not induce evident cardiorespiratory alterations. However, this procedure caused significant reductions in RBC, hematocrit, hemoglobin, and total plasma protein values. Seven weeks after bleeding, these parameters were recovered, and horses were ready for the next immunization/bleeding cycle. The intravenous administration of equine albumin, at a dose of 2 g/kg body weight, increased the apparent plasma volume and the albumin concentration. However, this procedure induced early adverse reactions and transient alterations of the serum levels of the enzyme gamma-glutamyl transferase (GGT), thus suggesting some degree of hepatic injury. It was concluded that immunization and bleeding as described in this work do not cause significant clinical alterations in the horse's health, except for a transient drop in some hematological parameters. The albumin-based fluid therapy used does not hasten the recovery after bleeding but instead induces adverse events in the animals.

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免疫、出血和白蛋白液体疗法在马身上的临床效果用作免疫球蛋白来源,以产生针对非洲蛇毒液的多特异性抗蛇毒血清(Echitab加ICP)
在蛇抗蛇毒血清的生产过程中,用作免疫球蛋白来源的动物会经历可能恶化其身体状况的过程。因此,必须仔细设计和验证这些条件。在这项工作中,评估了用于生产非洲多特异性抗蛇毒血清EchiTAb加ICP的马的免疫和出血方案对马健康的影响。这项研究的重点是之前用毒液免疫过的马,然后定期注射加强针以生产抗蛇毒血清。研究发现,用5 mg的Bitis arietans、Echis ocellatus、Dendroaspis polylepis和Naja nigricolis的静脉混合物进行周期性免疫,不会引起系统性的envenomation迹象,只会在注射部位引起轻度肿胀,不会发展成脓肿、瘘管或纤维化。连续三天出血,每天采集6-8升血液,并在第二天和第三天自行输注红细胞,没有引起明显的心肺功能改变。然而,该程序导致红细胞、红细胞比容、血红蛋白和总血浆蛋白值显著降低。出血七周后,这些参数得到恢复,马匹为下一个免疫/出血周期做好了准备。以2g/kg体重的剂量静脉注射马白蛋白,增加了表观血浆体积和白蛋白浓度。然而,这一过程导致了早期不良反应和血清γ-谷氨酰转移酶(GGT)水平的短暂变化,从而表明存在一定程度的肝损伤。得出的结论是,这项工作中描述的免疫和出血不会对马的健康造成显著的临床变化,除了一些血液学参数的短暂下降。所使用的基于白蛋白的液体疗法并不能加速出血后的恢复,反而会在动物中引发不良事件。
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来源期刊
Toxicon: X
Toxicon: X Pharmacology, Toxicology and Pharmaceutics-Toxicology
CiteScore
6.50
自引率
0.00%
发文量
33
审稿时长
14 weeks
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