Revisiting the acute kidney injury in Wistar rats experimentally envenomated wity Bothrops jararacussu venom.

There is no consensus on whether serotherapy prevents acute kidney injury (AKI) and there is no pharmacotherapy to impede the disease. We aimed to elaborate an AKI model induced by the administration of Bothrops jararacussu (Bj) venom for preclinical studies. Male Wistar rats were randomly divided into 3 different groups: (1) Bj-IV: intravenous administration of 0.4 mg/kg Bj; (2) Bj-IP: intraperitoneal administration of 2.0 mg/kg Bj; (3) Bj-IM: intramuscular administration of 3.5 mg/kg Bj. For each corresponding control group, a 0.9% saline solution was administered. Kidneys, blood and urine samples were collected 24 or 72 h after administration of the Bj venom for renal function analysis. The IV- and IP-Bj groups presented a moderate tubular injury (score 3) and a time-dependent kidney dysfunction. In the Bj-IM group, renal tubular injury was aggravated (score 4) with collagen deposition and renal dysfunction was observed in the first 24 h: hyperfiltration, proteinuria, albuminuria and decreased fractional sodium excretion (FENa), regardless of the administered dose. Over time, the glomerular lesion was intensified, with a decrease in glomerular filtration rate (GFR; 67%), blood urea-nitrogen (BUN; 68%) and urine volume decrease (71%). Proteinuria and tubular function returned to control levels after 72 h. We attributed the pronounced kidney injury and reduced filtration function in the Bj-IM to the muscle damage provoked by the IM administration. We concluded that the Bj-IM is the best preclinical model of AKI with the monitoring of the progression of renal function in the periods of 24 and 72 h.

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

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.