Doxycycline treatment reestablishes renal function of Wistar rats in experimental envenomation with Bothrops jararacussu venom

• Published in: Toxicon (Oxford) 2021-08, Vol.199, p.20-30
• Main Authors: Soeiro, Paula A., Romanelli, Mayara A., Cesar, Marcelo O., Nogueira-Souza, Pâmella D., Monteiro-Machado, Marcos, Oliveira, Simone S.C., Santos, André L.S., Melo, Paulo A., Lara, Lucienne S.
• Format: Article
• Language: English
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2021.05.008

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. [Display omitted] •Bothrops jararacussu (Bj) envenomation provokes kidney damage and impaired renal function.•Doxycycline inhibits in vitro proteolytic activity of the Bj venom.•Low dose of doxycycline administered 2 h after envenomation recovers renal function.•Low dose of doxycycline administered 2 h after envenomation preserves cortical (Na++K+)ATPase localization and activity.•Low dose of doxycycline administered 2 h after envenomation decreases renal metalloprotease activity.