Programa de Pós-graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil.
Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Toxicon. 2021 Aug;199:20-30. doi: 10.1016/j.toxicon.2021.05.008. Epub 2021 May 28.
Acute kidney injury is one of the main complications of ophidian accidents and the leading cause of death in patients who survive the initial damage effects of venom. The hypothesis proposed in this investigation is that the pharmacological repositioning of doxycycline (doxy) attenuates renal injury provoked by Bothrops jararacussu (Bj) venom. Male Wistar rats were subjected or not (control) to experimental envenomation with Bj venom (3.5 mg/kg, im). Doxy (3 mg/kg, ip) was administered 2 h after envenoming. Envenomation with Bj venom promoted tissue damage in the renal cortex (moderate degree, score 3) in 24 h associated with decreased glomerular and tubular function, which promoted proteinuria and polyuria. Doxy treatment prevented the increase in urinary volume in 3 times, the increase in plasma creatinine in 33%, the increase in blood urea-nitrogen accumulation in 65%, the increase in urinary Na excretion in 2 times, marked proteinuria and kidney cortex injury induced by Bj envenomation. Bj venom promoted increase in protein content (66%) and reduction of 45% (Na+K)-ATPase activity in the renal cortex. The enzyme was detected mainly in the luminal membrane. Doxy treatment was effective in preventing the mentioned alterations, maintaining (Na+K)-ATPase in the basolateral membranes.
急性肾损伤是蛇伤的主要并发症之一，也是幸存患者死亡的主要原因毒液初始损伤效应。本研究提出的假设是，多西环素（多西环素）的药理学再定位减轻了 Bothrops jararacussu（Bj）毒液引起的肾损伤。雄性 Wistar 大鼠接受或不接受（对照）Bj 毒液（3.5mg/kg，im）的实验性蛇伤。Bj 毒液中毒 2 小时后给予多西环素（3mg/kg，ip）。Bj 毒液中毒 24 小时后，肾皮质组织损伤（中度，评分 3）与肾小球和肾小管功能下降有关，导致蛋白尿和多尿。多西环素治疗可防止尿量增加 3 倍，血肌酐增加 33%，血尿素氮蓄积增加 65%，尿钠排泄增加 2 倍，Bj 毒液中毒引起的大量蛋白尿和肾皮质损伤。Bj 毒液促进肾皮质蛋白含量增加（66%）和（Na+K）-ATPase 活性降低 45%。该酶主要在腔膜中检测到。多西环素治疗能有效预防上述改变，维持（Na+K）-ATPase 在基底外侧膜中。
